1022-7954/00/3612- $25.00 © 2000
Russian Journal of Genetics, Vol. 36, No. 12, 2000, pp. 1344–1356. Translated from Genetika, Vol. 36, No. 12, 2000, pp. 1598–1613.
Original Russian Text Copyright © 2000 by Lilp, Bizikoeva, Revishin, Korochkin, Ivanov, Poletaeva.
Experimental biological models with morphofunc-
tional defects of the central nervous system (CNS) remain
an important source of information concerning patho-
physiological mechanisms of human CNS diseases. These
models should be developed to choose an adequate treat-
ment of patients and to conduct preclinical testing of the
pharmacological drugs improving CNS functioning.
Experiments with genetic models, i.e., animals with
hereditary defects of CNS, is one of the promising
approaches to many neurobiological problems .
These models include mutant, genetically uniform
inbred animals, as well as recently developed knockout
animals and transgenic laboratory mice [2–5]. The
main advantage of such genetic models is that they do
not require the invasive methods generally used in
physiology (for example, destroying of certain brain
regions), which often have side effects and make inter-
pretation difﬁcult. Moreover, neurogenetic and molec-
ular studies, which are impossible in humans, can be
performed with these models and gene–phenotype
associations can be established. Although many neuro-
genetic models have been developed by now, each new
neurological mutation or animal strain is unique and
interesting for analysis of genetic factors determining
CNS development and functioning.
Our studies showed that the 101/HY mice represent
an attractive and promising neurogenetic model. This
mouse strain was obtained by Dunn in 1936. In 1969,
the animals were transported from the Radiobiological
Center in United Kingdom to the Soviet Union but the
information concerning the duration of inbreeding was
not available. Since then, the strain is maintained in the
collection of the Laboratory of Experimental Biologi-
cal Models, Russian Academy of Medical Sciences.
After several dozens of generations of inbreeding
passed, the strain was termed 101/HY (Y-Yurlovo) .
As compared with mice of other strains studied, the
101/HY mice showed genome instability, which was
manifested by the high level of spontaneous chromo-
somal aberrations in germline and somatic cells [7–9].
In addition, the 101/HY mice were shown to be
extremely sensitive to the teratogenic effect of alkylat-
ing compounds, which resulted not only in increased
frequency of the skeletal system developmental
defects, but also in the more pronounced behavioral
deviations in adult animals as compared to mice of
other strains [10, 11].
This paper is dedicated to the 10th anniversary
of the Institute of Gene Biology, Russian Academy of Sciences
Behavioral, Neurochemical, and Brain Morphology Features
of the 101/HY Mice: A Genetic Model
of Some Human Hereditary Diseases
I. G. Lilp
, F. Z. Bizikoeva
, A. V. Revishin
, L. I. Korochkin
, V. I. Ivanov
, and I. I. Poletaeva
Institute of Human Genetics, Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow,
115478 Russia; fax: (095)324-07-02; e-mail: firstname.lastname@example.org
Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, 117071 Russia
fax: (095) 135-97-83; e-mail:email@example.com
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 117334 Russia
fax: (095) 135-25-41; e-mail: firstname.lastname@example.org
Biological Faculty, Department of Higher Nervous Activity, Moscow State University, Moscow, 119899 Russia
fax: (095) 939-44-68; e-mail: email@example.com
Received March 29, 2000
—Studies of behavior, neurophysiological reactions, neuromediator synthesis and brain structure of
mice of the 101/HY strain (including those of the authors) are reviewed. This mouse strain is characterized by
a chromosomal instability because of a recessive mutation
and the defective DNA excision
repair. Experimental studies revealed a number of behavioral and neurological deviations in the 101/HY as
compared to the CBA and the C3H mouse strains. These are abnormalities in spatial orientation, altered fear
and anxiety reactions, anomalous locomotion, seizure developing in response to agents of various nature, and
disturbances of the central nervous system, both structural and biochemical. Genome instability results in a
number of neurological mutations, that may lead to the phenotypical effects observed in the 101/HY mice.
Since the 101/HY mice partially display signs of severe human hereditary diseases caused by chromosomal
instability and defective DNA repair, they can serve as a promising genetic model for these and other diseases
related to impairment of the central nervous system.