TY - JOUR
AU - Farmer, Susan C
AB - Abstract The use of aquatic animals in ecotoxicology, genetic, and biomedical research has grown immensely in recent years, especially due to the increased use of zebrafish in the laboratory setting. Because water is the primary environment of most aquatic species, the composition and management of this water is paramount to ensuring their health and welfare. In this publication, we will describe the important variables in water quality that can influence animal health and research results, using the zebrafish model for detailed specifics of optimal conditions. Wherever possible, recommendations are provided to reduce the potential impact of poor or highly variable water quality, and standards are given which can be used as institutional goals to maximize animal health and welfare and reduce research variability. It is increasingly important that authors of publications describing work done using aquatic models characterize water quality and other environmental conditions of the animal environment so that the work can be repeated and understood in context of these important factors. It is clear that there are a great many extrinsic factors which may influence research outcomes in the aquatics model laboratory setting, and consequently, an increased level of funding will be essential to support continued research exploring these and other important husbandry conditions. References from a large body of literature on this subject are provided. aquatic models, husbandry, water quality, zebrafish Introduction/Overview Fish are the oldest class of vertebrates, arising more than 500 million years ago. They make up more than one-half of all vertebrate species (+32 000), in fact more than all the other classes combined (+60 000) [1]. Perhaps a dozen or so of these fish species are of particular interest with respect to the field of laboratory animal models [2]. Amphibians arose around 370 million years ago and include around 7000 species, of which only a few are commonly found in this field [3]. Over the last 30 years, the zebrafish (Danio rerio) has become the preeminent aquatic animal model used in biomedical research. This is due in large part to its robust nature, small size, ease of observation during embryonic development, amenability to mass culture, and ease of genetic manipulation. Because of its prevalence, much of the reported information about the impacts of housing conditions and husbandry practices on research outcomes in aquatic models derives from the zebrafish field. While the most recent (8th) edition of the Guide for Care and Use of Laboratory Animals [4], published in 2011, contains a 12-page section dedicated to aquatic animals, it makes no strong statements regarding specific husbandry practices, ranges of tolerance, or guidelines for water quality of common aquatic animal models as it does for many of the common terrestrial animal models. This condition is bound to change provided that we continue to report our husbandry practices in the most thorough way possible when research is published, and if we continue to insist that funding and resources be made available to further our understanding of these conditions and the influence they have on research outcomes. In 2010, the ARRIVE Guidelines for Reporting Animal Research [5] were developed to encourage sharing of information on conditions of husbandry used in experiments in an effort to increase standardization/repeatability and reduce variation. Additionally, the National Institutes of Health recently began encouraging similar practices to those described in the ARRIVE Guidelines in order to encourage reproducibility in research results and reduce variation between experiments [6]. The culture conditions of the laboratory zebrafish at various stages of life are subject to variation, both unintentional and by design. In some cases, we have a clear understanding of how changes or deviations from typical culture conditions can impact fish health and experimental outcomes; however, in many cases we do not. While much of the historical research using zebrafish has focused on the embryonic and larval life stages, there exists a growing body of work focusing on characteristics of the post-metamorphic and adult life stages, such as behavioral research and age-related disease [7,8]. In the case of the embryonic life stages, much of the variability can be eliminated by utilizing commonly used recipes for media and adhering to good laboratory practices where housing of embryos is concerned. However, in the case of fish housed in communal, recirculating aquaculture systems, extrinsic factors such as water quality, noise and vibration, lighting conditions, and housing density are often dictated by the facilities available and the policies of the institutions in which they are housed and maintained. Water quality is defined by a range of physical and chemical parameters and is perhaps the most important factor when considering the management and maintenance of aquatic species. Water provides fish with oxygen, allows for waste removal, and is the conduit for their food. The temperature of the water will influence the fish’s body temperature and therefore will influence its metabolism and physiology. However, due to the differing requirements and ranges of tolerance of various aquatic species, the term “water quality” has the potential to become vague unless we provide the context of a specific species and the life stage of concern. Consequently, much of what follows will focus on the larval and post-metamorphic life stages of the zebrafish. For those aquatic animals such as zebrafish used to model human diseases, it is imperative that environmental and husbandry conditions are well defined and described so they do not introduce variation into the experimental results. Husbandry professionals and facility managers can minimize variability by striving to maintain the highest degree of stability in those environmental conditions under their control, chief among them being the various water quality parameters discussed in this review. Scientists must understand how these conditions may alter results, and this should inform and influence experimental design. It is critical that all relevant parameters be regularly measured and these results documented so they can be assessed as part of the interpretation of findings. It is also important that this information be reported in publications so that repeatability is enhanced. Water Quality Source water The term “source water” describes the water used to create the aquatic environment for zebrafish culture operation. This water may originate from a well or bore that draws water from an aquifer or, most commonly, from a municipal water source originating from surface or ground water that is treated to make it safe for human consumption. Because all the decisions about water purification and conditioning are dictated by the physical and chemical qualities of this source water, it bears significant consideration when designing a zebrafish facility. In most biomedical research facilities, source water must be purified before it can be used for fish. The most common purification methods are reverse osmosis and deionization, and in some instances, both of these treatments are used in tandem. Reverse osmosis water is created by forcing water under pressure through a semi-permeable membrane with small pores against a concentration gradient to remove impurities; this process often requires substantial pretreatment such as softening, tempering, and activated carbon and involves the use of high-pressure pumps. Deionization water is created by exchanging positive hydrogen and negative hydroxyl molecules for positive and negative dissolved minerals and solids in the source water. These treatment processes yield a product of such high purity that it is unsuitable to use as a direct medium for fish. Consequently, it is necessary to condition this water by adding both salt ions and buffers in a controlled manner to make it suitable for the fish. This may be done in a batch approach whereby specific volumes or quantities of “fish-ready” water are prepared or, perhaps most commonly, the recirculating zebrafish system is topped up after experiencing a planned water exchange. In this case, the buffer and salt solutions are added directly to the system as the continuous monitoring and controlling equipment respond to deviations from the programmed set points. While the majority of zebrafish systems used in biomedical research are of a recirculating nature (RAS), there are some situations where a single-pass or flow-through system is used. Because of the prevalence of RAS, the majority of this review will concentrate on these systems. Chlorine and Chloramine Chlorine and chloramine are chemicals often used in the disinfection of municipal water and for disinfection of embryos and some surfaces and equipment in zebrafish facilities. Chlorine is toxic to freshwater fish, including zebrafish, and may cause acute fatalities at concentrations as low as 0.15 mg/L [9,10]. Chloramine, a stable compound comprised of chlorine and ammonia, has been shown to be lethal to fish at concentrations as low as 0.19 mg/L [10]. The stability and efficacy of chloramine as a disinfectant for municipal drinking water has led to an increase in the prevalence of its use, and this must be considered when provisioning the water purification equipment for zebrafish facilities. Effectively neutralizing chloramine requires a specialized type of granular activated carbon (GAC) known as catalytic GAC. Catalytic GAC is generally made by treating activated carbon by pyrolysis, that is, exposure to very high temperatures in the presence of nitrogen-containing compounds (ammonia or urea). This results in an increase in its surface area, more numerous and more accessible active carbon sites, and the presence a very specific active nitrogenous site that ordinary GAC does not have. These changes, which increase the efficiency of the GAC for breaking the chlorine-ammonia bond, are necessary for removal of chloramines [11]. There are also commercially available water conditioners and/or substances, such as sodium thiosulfate, that neutralize these chemicals, but it should be understood that these chemicals make resultant compounds that may not be desirable from a fish or human health standpoint. Although many recirculating zebrafish systems may incorporate GAC filtration as a part of their flow process, unless they have been specifically designed and appropriately sized to remove chlorine and chloramine, they may lack the surface area and contact time necessary to adequately neutralize chlorine and chloramine concentrations found in municipal water sources. For this reason, GAC filters on zebrafish systems should not be relied on to avert injury to or loss of fish in the event of a chlorine/chloramine contamination event. The GAC filters found on recirculating aquaculture systems such as those designed for zebrafish are best suited for the removal of tannins to maintain optimal water clarity and adsorption of some dissolved organic compounds or contaminants resulting from metabolic processes or the degradation of RAS components (plastics, metals, etc.) and require regular maintenance and replacement of the media to remain effective at their intended purpose. pH Power of hydrogen, or pH, is defined as the negative log of the hydrogen ion concentration in the water (− log [H+]). Zebrafish are found in natural environments with water varying in pH from 6.6 to 8.2 [12,13]. The optimal pH for zebrafish husbandry has not been determined empirically; however, the LC50 for acute exposure for 72 hours has been shown to be at a low of 3.9 and at a high of 10.8 [14]. Most zebrafish facilities strive to maintain their fish water at or near pH 7.5. pH has been demonstrated to influence other water quality parameters, such as ammonia, where as the pH of the water increases, so does the toxic fraction of ammonia. High- or low-pH levels can lead to a number of problems, including excessive mucus production, loss of sodium and chloride ions, increased cortisol levels (stress), loss of acid/base balance, loss of normal swimming behavior, hypoactivity, convulsions, and death [14]. Changes in gene expression have also been noted [9,14,15], and zebrafish raised at extremes of their pH tolerance can suffer from damaged gill epithelium [14]. Nitrogenous wastes Nitrogenous wastes are produced in recirculating water systems by normal metabolic function of the fish housed therein and by decomposition of uneaten food and other detritus. Nitrogenous wastes include ammonia, nitrites, and nitrates. Ammonia, or more precisely, total ammonia nitrogen (TAN), represents the sum total of the less toxic ionized ammonia (NH4+), and the toxic un-ionized ammonia (NH3). Ammonia (TAN) is the primary waste product of fish metabolism as it is excreted across the gills [16] and, to a lesser extent, found in the feces. It is also produced when uneaten food decomposes, and for this reason, it is important to consider the types of foods offered to the fish as well as the frequency and amounts offered. It is preferable to distribute the feedings into more than 1 ration over the course of the day to minimize the accumulation of uneaten food and feces and the severity of the resultant increase in ammonia concentration [17]. The toxicity of NH3 is influenced by pH and temperature. At higher temperatures and pH, the toxicity of NH3 increases, which can affect fish physiology and the reaction of fish to anesthesia. While in nature the nitrogen cycle consists of several different processes, nitrification is the primary process whereby ammonia is ultimately converted to less toxic nitrate. In recirculating aquaculture systems like those used in zebrafish facilities, nitrification is carried out by bacteria harbored in specialized bio-filters. These bacteria can also be found growing in other parts of the recirculating system, such as in gutters and on tank surfaces. In practice, the level of TAN in zebrafish systems should be maintained at 0.0 mg/L. Nitrite (NO2−) is the product of the first step of nitrification by bacterial oxidation of un-ionized ammonia and is toxic to fish at levels as low as 0.1 mg/L [9]. High concentrations of nitrite can change the shape of hemoglobin and reduce its ability to transport oxygen, resulting in a condition called brown blood disease, which eventually causes suffocation if not remedied quickly [9]. Chronic exposure to low levels of nitrite can result in immunosuppression and make fish more susceptible to bacterial infections, and high levels of mortality may ensue [18]. In practice, the level of nitrite in zebrafish systems should be maintained at 0.0 mg/L. Nitrate (NO3−) is the product of the second and final step of nitrification by bacterial oxidation of nitrite. While less toxic, nitrate is not harmless to zebrafish. Zebrafish exposed to nitrate at >400 ppm showed reduced growth, survival, and development, and at levels as low as 100 mg/L, zebrafish displayed abnormal histology results [19]. To avoid the accumulation of nitrate, most recirculating fish systems employ regular, periodic water exchange whereby nitrate (and other pollutants) laden water from the system is disposed of and is replaced with high-purity or fish-ready water. The laboratory zebrafish field most commonly uses a 10% water exchange as a standard, which should be distributed throughout a 24-hour period (eg, hourly). However, some situations may require regular water exchange in a greater overall volume, while other systems may perform perfectly well (from a water quality standpoint) at much lower exchange rates. It is critical to make adjustments to this water exchange rate based on changes in system biomass, feeding practices, fluctuations in total system volume (addition/removal of fish tanks), and the results of daily water chemistry testing. For example, when increasing or decreasing the number of fish (biomass) held on the system, the volume of water exchange should be adjusted to reflect this change but with the goal of maintaining the existing daily water exchange rate (percentage). Temperature Like the majority of fish, zebrafish are poikilotherms (cold-blooded), and, consequently, temperature is an important environmental variable of their culture conditions. The accepted standard temperature for studying the development of zebrafish embryos is 28.5°C [20], and deviations in environmental temperature from this standard will lead to increased or decreased developmental rate, creating the potential to confound the results of developmental studies. Incubators used to house zebrafish embryos should be set to 28.5°C, tuned to prevent under- or over-heating, and monitored using temperature loggers and alarms where possible. Refrigerated incubators should be considered if the ambient temperature of their location is within 5°C of the set point. While zebrafish are highly eurythermal, exhibiting an acclimated thermal range of tolerance from 6.2°C to 41.7°C [21], larvae and adults in the biomedical setting should be kept at a stable temperature within the range of 24–28°C [22]. Increased temperatures will increase metabolic rates of larvae and adults, which will increase food consumption, respiratory rate, and waste production, while decreased temperatures will have the opposite effect. Increased environmental temperatures can also affect sex determination in fish through various pathways, such as female-to-male sex reversal [23]. Increased water temperature may also affect water quality. For example, oxygen saturation decreases with increased water temperatures, and the amount of toxic ammonia increases with increasing temperature. Most recirculating zebrafish systems are provisioned with submersed electric heaters and therefore can be programmed to maintain virtually any set point above ambient laboratory temperature. Although less commonly provisioned for typical zebrafish systems, chillers are available for reducing the temperature if the situation requires it. Salinity and Conductivity The terms “salinity” and “conductivity” both are related to the ionic content of the water, but they are measured differently as described below. Salinity is defined as the total concentration of all ions dissolved in water. Zebrafish exhibit a tolerance of salinity ranging from less than 0.2 g/L to 14 g/L [24], but in practice salinity should be maintained at a stable level within the range of 0.5–2.0 g/L [25]. Maintaining salinity at either end of the range of tolerance may have undesirable consequences on embryos such as accelerated hatching [26] or delayed hatching [24]. In post-metamorphic forms, consequences may include altered social behaviors [27], damaged gills, and reduced nitrogen excretion [28]. Specific conductance, or conductivity, describes the ability of a material or solution to conduct electricity and is defined in this context as the amount of dissolved salts or ions in water. In the wild, zebrafish have been found in water with conductivity ranging from 10 to 2000 micro Siemens [13,29]. In typical zebrafish systems, conductivity can range from 100 to more than 2000 micro Siemens, depending on the desires of the culturist. While an appropriate level of ions is necessary to support osmotic and ionic regulation of the fish, if ion levels are too high or too low, fish will have to expend excessive energy to manage tissue hydration necessary for normal physiological function, which will consequently result in reduced growth and fitness. Ionic stress can lead to adverse outcomes in embryos such as premature hatching and reduced survival [26]. Many zebrafish culturists maintain conductivity using the addition of a “reef salt” designed to emulate the conditions of a coral reef or marine fish environment for marine aquarium hobbyists. This approach is attractive due to the availability of such products; however, it fails to consider that freshwater fish do not live in diluted seawater and that the proportions of many of the other salts and buffers in these highly proprietary formulations are not known to be favorable to freshwater fish physiology. These reef salt mixes also carry a high financial cost and unknown influence on normal metabolic and physiologic function of zebrafish at various life stages. A suitable alternative exists in the form of high-purity NaCl (+99.9%), which is readily available at a fraction of the cost of reef mixes. Formal studies defining an optimum range of conductivity and ionic composition would be valuable and could be rooted in a review of the ion composition and concentrations in the natural range of zebrafish as well as a formal review of values reported in existing literature and surveys of existing zebrafish facilities. Hardness Hardness refers to the amount of divalent ions (Ca+2, Mg+2, Fe+2, Mn+2, Sr+2) present in fish water. These ions, especially calcium, are essential for the formation and maintenance of bones and teeth, muscle contraction and nerve function, blood clotting, osmoregulation (water/salt balance in tissues), and embryo production and viability. Like most aquatic organisms, zebrafish get these ions from both water and their diet. If hardness is not consistently maintained at an appropriate level, metabolic energy will be used to compensate, which may redirect energy away from the important functions of growth and development. Zebrafish have been classified as a “hard water” species, likely due to the calcareous nature of the geology where they have been collected in the wild. This means that they prefer hardness values of 100 mg/L CaCO3 [30]. Perhaps the simplest way to increase hardness in a zebrafish system is by incorporating a bed or reactor of calcium carbonate (CaCO3), such as aragonite sand, or crushed coral inside a fish tank that is on the system, or in a purpose-built reactor. As water contacts these substrates, the calcium carbonate is dissolved into its constituent elements, calcium and carbonate, and goes into the water. This media will need to be periodically refreshed as it dissolves but can provide an inexpensive, long-lasting, and highly effective means of increasing hardness (and alkalinity). In practice, a minimum of 75 mg/L should be maintained in zebrafish culture systems. Alkalinity Alkalinity, usually expressed as milligrams per liter of CaCO3, refers to the amount of all bases present in water and reflects the pH-buffering capacity of the solution. Factors, including fish respiration and metabolism and biological filtration (nitrification), produce acids and reduce pH. When this occurs, the availability of carbonate (CO3−) and bicarbonate (HCO32−) ions in the water will determine how low the pH will drop. The availability of bicarbonate is crucial for the survival and growth of the nitrifying bacteria that populate the bio-filter, and its deficiency can result in sudden increases of ammonia in the system. In practice, it is advisable to maintain the water in a typical zebrafish system at between 50–150 mg/L CaCO3. Many zebrafish systems employ sodium bicarbonate as the primary source of alkalinity, but in most cases this is inadequate to maintain the desired concentration of CaCO3; an additional source, such as aragonite (crushed coral), should also be used. Dissolved Gases Several atmospheric gases are normally found dissolved in fish water. Chief among these is oxygen. Warm-water, freshwater fish require a minimum of 4 mg/L for normal growth and physiological function [31], and biological filtration requires a minimum of 2 mg/L [32], but in practice dissolved oxygen should be maintained at or near saturation (approximately 7.8 mg/L at 28°C). Aquatic hypoxia is considered a teratogen, and thus exposure to inadequate levels of dissolved oxygen can lead to malformations [33] and changes in embryonic gene expression [34] as well as a prevalence of male-dominated sex ratios in laboratory populations [35]. CO2 gas is excreted during respiration and, if allowed to accumulate, will decrease the pH of the water through the formation of carbonic acid. High concentrations of CO2 have a narcotic effect on fish, causing them to appear disoriented [36]. Supersaturation of water with atmospheric gases, primarily nitrogen and oxygen, occurs when the concentration of dissolved gases exceeds 100% total gas pressure and most often results from a plumbing or mechanical failure. Supersaturation in excess of 103% can cause gas bubble disease (GBD) resulting in very rapid high mortality [37]. In the case of GBD, fish will absorb these gases (mostly nitrogen) into their tissues and body fluids, and when the gases are released in the form of bubbles, tissue damage occurs [38,39]. Probes are available to continuously monitor total dissolved gas pressure when integrated into modern RAS housing aquatic models. These probes can be programmed to respond to elevated gas saturation events by alerting the husbandry staff and stopping the flow of water to avert mass mortality due to GBD. Solid Wastes Recirculating aquaculture systems like those used in zebrafish facilities have a high degree of effluent that will contain dissolved, suspended, and settleable solids. All of these solids can deteriorate favorable water quality conditions if allowed to accumulate. Dissolved solids are smaller than 2 microns and may affect water color and clarity. These often originate from the pigments found in formulated fish feeds and from the algae commonly found growing in the RAS. These solids are eliminated from the recirculating fish systems through water exchange and with the use of chemical filtration means such as GAC. Suspended solids are larger than 2 microns in size and are removed from the recirculating system either through water exchange or a mechanical filtration method such as filter socks or screens. If the concentration of these suspended solids is great enough, fish health can suffer due to gill damage. While to our knowledge there has been no definitive work establishing the acceptable range of suspended solids for zebrafish, it has been shown that levels as low as 50 mg/L can result in structural gill damage in the green grouper [40]. It is thus recommended to keep suspended solids as low as possible in recirculating systems. Larger suspended solids are considered settleable solids and will drop out of suspension if an adequate reduction in water velocity is available, such as where return plumbing enters a large sump. An increased load of any of these solids in the water leads to increased biochemical oxygen demand and can also result in increased nitrogenous waste levels. Observed accumulations of these settleable solids should be regularly removed using manual methods such as a siphon apparatus. Biofilm, Algae, Cyanobacteria Biofilms, algae, cyanobacteria, and bryozoans may be commonly found in zebrafish facilities and, while not necessarily desirable, may be considered incidental co-culture organisms. Biofilms, algae, and cyanobacteria are commonly found growing on wet surfaces, such as the inside surfaces of fish aquaria, where both light and nutrients (nitrogen) are readily available. Once established, they are nearly impossible to eliminate completely. They can be reduced with sound feeding practices, routine tank exchanges, careful water quality management, minimization of intense lighting, and adherence to strict quarantine, biosecurity, and environmental hygiene plans. These steps will limit their growth and impact in the facility. It is advisable to implement a regular tank exchange interval to minimize the impact of these organisms on the performance of the self-cleaning design of the fish tanks typically used in zebrafish facilities. There exists no standard tank exchange interval in the zebrafish field at this time; rather, we rely on more arbitrary measures such as reduction in tank function or optical clarity of the viewing panes of the tanks to signal the need to perform tank exchange. Historically, much of the cage wash performed on aquatics caging and related equipment has been performed manually, but in the last decade, specially designed, automated cage-wash equipment, mirroring that which is standard equipment in rodent facilities, has made the safe and effective removal of algae, biofilms, and bryozoans possible. Considering the time and resources required to wash equipment manually and the availability of automated equipment, it is advised that this technology should be carefully considered for all new zebrafish facilities and for many existing facilities. Indeed, if a designer proposed to build a rodent vivarium without including automated washing equipment, it would not even be considered. Biofilms are an aggregate of microorganisms in which cells that are frequently embedded within a self-produced matrix of extracellular polymeric substance adhere to each other and/or to a surface [41]. In the aquaculture setting, several studies have demonstrated that the self-produced matrix, or lattice, is capable of harboring pathogens such as Vibrio spp. and Mycobacterium spp. and parasites such as Myxidium streisingeri [42,43]. Some pathogens, such as Flavobacterium columnare, are capable of creating biofilms themselves [44]. Indeed, the chemotrophic and heterotrophic bacteria responsible for colonizing RAS biofilters are biofilm-forming bacteria. Biofilm may accumulate to an extent that it obscures the view of the fish in the aquaria, and it can even impede proper function of the tanks by mechanically blocking water flow into or out of the tanks. Brown algae are commonly found in zebrafish housing aquaria and can similarly pose problems when they cover tank surfaces and obscure our ability to perform required daily health checks. When their growth reaches a critical threshold and obscures the optical clarity of the aquaria, the tanks should be exchanged. Filamentous algae pose a threat to not only our ability to view the fish in their aquaria, but they can act as a bio-fouling agent and impede the flow of water into and out of the aquaria. These algae take advantage of both light and nitrogen available in the recirculating system and are best prevented from accumulating through practicing good water quality management, limiting high-intensity lighting, and avoiding overfeeding practices. Cyanobacteria, also common in freshwater recirculating aquaria, are perhaps less benign since some are known to produce neurotoxins, hepatotoxins, and dermatoxins. Although no confirmed cases of occurrence in zebrafish facilities have been reported, in experimental settings zebrafish have demonstrated increased anxiety and stress levels (whole body cortisol) as well as deviations in normal swimming behavior [45] when exposed to one such cyanotoxin, microcystin-LR. Additional studies using the cyanotoxin beta-Methylamino-L-alanine have shown a negative impact on early neuronal development, which has implications for those researchers studying neurodegeneration disorders such as Amyotrophic Lateral Sclerosis, Alzheimer’s, and Parkinson’s like-dementia [46,47]. Because zebrafish are commonly used as models in the fields of eco-toxicology and development and in modeling human disease, it is of particular importance that cyanobacteria are identified quickly in the zebrafish laboratory and that through good water quality management practices, toxin-producing blooms are prevented. It is important to note that these toxins not only have the potential to negatively affect research but can also harm the health of husbandry staff members who work in zebrafish facilities if they ingest or inhale aerosols containing these toxins. Bryozoans are animals whose presence in the fossil record dates back to at least 480 million years ago [48]. Because of their morphology, they harbor many other organisms, some of which may be pathogenic or parasitic to zebrafish, including Episylis sp. and Stylaria, which are themselves also potential hosts for myxozoans [25]. Perhaps the most important threat that these organisms pose to the daily operations of zebrafish facilities is as a bio-fouling agent. Bryozoan species such as Plumatella repens can quickly and firmly establish themselves inside aquaria and supply/return plumbing, thereby causing significantly reduced performance of the “self-cleaning” action of modular aquaria and the flow and filtration processes of a recirculating system; they also have a strong and unpleasant odor (personal observations). It is in the best interest of facility operators to prevent bryozoans from entering their facilities through adhering to strict quarantine and biosecurity policies. In the event that bryozoans do become established in a facility, it is important to maintain good water quality and feeding practices that prevent an abundance of nutrition for the bryozoans and to exchange tanks as soon as the offending organisms are observed. Unfortunately, at this time, it is very difficult to impossible to remove bryozoans from a recirculating water system once they are present, and at this time there is no good way to do this without completely decommissioning and disinfecting the system. Lighting and Illumination An aspect of zebrafish husbandry and welfare that may hinge completely on laboratory design and equipment selection is that of lighting and illumination. Although evolution on the surface of the planet occurred exclusively under the full spectrum of natural sunlight [49], such lighting conditions are currently impossible to replicate in the larger laboratory setting. Fortunately, a growing body of research is beginning to elucidate the effects of lighting qualities on basic biological and physiological processes as well as direct impacts on research outcomes for embryonic, larval, and adult zebrafish [50–52]. Light source. Many zebrafish facilities are lighted exclusively by fluorescent tubes, which are often selected without thought to their potential effects on zebrafish or research but with the husbandry and research staff as the primary consideration. With the advent of energy-efficient, affordable, and programmable LED lighting, designers began to consider them when designing zebrafish facilities and selecting incubators. However, little is currently known about whether a shift away from fluorescent lighting is warranted by the lighting quality on offer or whether it is justified by any potential cost reduction resulting from LED energy efficiency. Light intensity. It has been suggested that a broad range of lighting intensity (54–324 lux) is appropriate [22], but a growing body of work is beginning to demonstrate that light intensity can have demonstrable effects on research outcomes in zebrafish [53–55]. From a practical standpoint, light intensity must be adequate for husbandry and veterinary staff to perform their required daily health checks and for fish to be able to detect food items. However, it must not be so bright as to create a situation where algal growth is encouraged, resulting in an unsustainable increase in the need for cage wash and exchange develops. Spectrum and wavelength. Color temperature is a descriptor often used by lighting manufacturers (ie, cool white is approximately 4100 K) and is actually more indicative of the spectrum of light produced by a light source. The spectrum of wavelength is perhaps just as important as any of the other qualities of lighting because zebrafish are capable of perceiving light well outside the range perceived by humans [51]. Often, lighting color is chosen as a consideration for technicians working in the environment and perhaps in an effort to provide the best lighting color possible to assist in the manual task of sorting male and female fish for spawning crosses. To this end, it is advisable to select a light color closer to that of natural sunlight. While the research continues to accumulate on the effects of lighting wavelength and spectrum, not all of it is in agreement [56]; thus, more experiments and a larger body of data are warranted. Photoperiod. A regular and uninterrupted photoperiod has long been understood as a critical aspect in successful spawning of zebrafish. There is a growing body of research describing its impacts on feeding and growth [57–59], embryonic development and survival [60], sleep [61], and behavior [54,57]. It is not uncommon for zebrafish facilities to employ a 14-hour light:10-hour dark photoperiod; others may prefer a 12-hour light:12-hour dark photoperiod, but because zebrafish reproduction depends strongly on photoperiod, whichever is chosen, it should remain consistent to avoid interruptions in regular egg production [62,63]. Because the zebrafish constitute perhaps the single best animal system in which to study the complexity of the circadian clock machinery and the influence that light has on it [64,65] and because of the broad overall impact that different aspects of lighting quality have on zebrafish welfare, continued and vigorous research on lighting qualities is essential if any standard or consensus is to be determined. Further studies of the importance and effects of light qualities in zebrafish facilities that make use of our existing knowledge about the ways in which zebrafish process light and color [66] are certain to be of great value. Zebrafish Housing Aquaria Zebrafish are commonly housed in small (10 L or less), modular tanks, often constructed from polycarbonate plastic. While less common, glass, fiberglass, and other plastics are available for these aquaria, often in different enclosure shapes (such as round) and sizes; some of these may provide a distinct advantage for particular research or husbandry goals, such as behavioral studies or spawning and genetic management of stocks. Much discussion has surrounded housing density (ie, number of fish per liter of tank volume), with most consensus centering around the adult life stage and focusing most concern on the potential to create a situation where dissolved oxygen is critically limited or where aggression is elevated and unchecked [67]. Increased aggressive behaviors tend to occur at either end of the stocking density spectrum. That is, when fish are housed in low numbers (ie, <5 fish total) [68] or at densities <40 fish per liter [67,69] or where the overall volume of water is inadequate for schooling behavior to develop naturally, either the level of aggression and or the level of cortisol production may create health and welfare concerns for zebrafish [67]. In either case, the addition of physical habitat enrichment (ie, artificial plants) may ameliorate the stressful conditions [70–72]. Other authors have noted, however, that provision of excessive vegetation can also induce a stress response and increase aggression of zebrafish [73,74]. There are also publications implicating housing density as affecting sex determination [75]. When housing fish on recirculating aquaria, the flow rate of water can be of specific concern. The flow rate must be adapted for the life stage (relative size and swimming ability) of the fish in question. Flow rate must be of an adequate nature to remove waste products from the tank and provide an influent consisting of fish-ready water in which dissolved oxygen is at or near saturation. Because zebrafish in the wild are often found in slower-moving water [13] and in the laboratory have demonstrated a preference for moving water over static [72], we can infer that the proper flow rate must be achieved without creating a water current velocity too strong for the fish to swim against. Spawning tanks are most often static (no flow), small enclosures (<2 L) and must be closely monitored to avoid injury or death of fish due to water quality deterioration or elevated aggression from housing the fish in this setting. These smaller crossing tanks are best suited for pair-wise crosses and small group crosses consisting of only a few fish. The use of mass-spawning tanks integrated into the recirculating system is becoming increasingly common, and there are some indications that the elevated stocking density, coupled with the availability of shallow areas in which females can deposit eggs, is a large part of why they can be so successful [76]. Noise and vibration are environmental factors found in all zebrafish facilities. The various pumps and other equipment that make it possible for us to house and maintain large numbers of fish tanks carry with them inherent noise and vibration. Add to this the infrastructure of the buildings where these facilities are often located and the normal daily activities of husbandry and research staff, and you begin to understand that it is not surprising that the soundscape of the laboratory is vastly different from that of the natural habitats of zebrafish in the wild [77]. Excessive vibration, as from a pump that is inadequately isolated from the structure of a typical zebrafish rack, can negatively affect the spawning performance of zebrafish and suppress appetite and normal swimming and social behavior (personal observation). Low-frequency vibrations have been shown to induce patterning defects in both Xenopus and zebrafish embryos [78]. Additional studies have demonstrated that zebrafish exhibit clear responses to different types of auditory stimuli and, in some cases, may support the use of auditory enrichment to reduce stress in zebrafish [79,80]. Because noise and vibration are virtually unavoidable in the laboratory setting and because zebrafish have exhibited a hearing sensitivity range of 200–4000 Hz [81], it is important that additional research be performed with the goal of establishing some firm guidelines to better inform facility designers and managers. Conclusions/Summary Since the 1998 publication of Care and Use of Fish as Laboratory Animals: Current State of Knowledge by Casebolt et al [82], there has been a significant increase in the number of publications where zebrafish feature as a model organism, and substantial advances in our knowledge of the husbandry and care of aquatic models have been made. However, this progress is perhaps not commensurate with the sheer bulk of zebrafish (and other aquatic models) based research being conducted or published. It is clear that the laboratory setting is rife with potential extrinsic factors that influence research outcomes where aquatic models are concerned. It is even clearer in the light of the serious lack of standardization of husbandry practices within these facilities. Consequently, it is imperative that funding be made available to improve our knowledge and understanding of these variables and their influence on the massive efforts made where aquatic animals feature as the primary model systems work. More animal husbandry and animal health professionals are needed to carry out this work and to create robust experiments with outcomes that can be used to propel our practices of animal husbandry and welfare into the coming decades. It is also critical that a baseline set of husbandry and water quality parameters specific to that animal culture facility be reported each and every time that an aquatic species such as zebrafish is used as a model organism in biomedical and other scientific research. Like most living systems, abrupt changes in our environmental conditions usually result in an increase in stress. 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TI - Aquatic Models: Water Quality and Stability and Other Environmental Factors
JF - ILAR Journal
DO - 10.1093/ilar/ilaa008
DA - 2019-12-31
UR - https://www.deepdyve.com/lp/oxford-university-press/aquatic-models-water-quality-and-stability-and-other-environmental-jiffocSv7b
SP - 141
EP - 149
VL - 60
IS - 2
DP - DeepDyve
ER -