Genetic comparison between laboratory rats and Japanese and
German wild rats
Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 Japan
Department of Laboratory Animal Science, Institute of Pathophysiology, University of Greifswald, Karlsburg 17495, Germany
Received: 29 February 2000 / Accepted: 10 April 2000
The history of the rat as a laboratory animal began in the 1850s.
Researchers from France (Philpeaux 1856), England (Savory
1863), and Germany (Crampe 1877) pioneered the use of rats as
experimental animals. However, the beginning of rat breeding for
scientific purposes can be traced to North America, as virtually all
inbred rat strains in the world today may attribute their ancestry to
stocks in the United States. The Wistar rats, which were brought to
the Wistar Institute by Donaldson in 1906, have played an espe-
cially important role in the development of laboratory rat strains.
The origin of this key strain is unknown, as Donaldson himself
acknowledged (Donaldson 1912a, 1912b). As nearly all contem-
porary laboratory rat strains have been bred for a number of de-
cades apart from their wild-type comrades, it may be assumed that
wild rats and laboratory rats could have developed dissimilar ge-
netic allele patterns. The wild rats of different geographic locations
may have different alleles, as well. These assumptions prompted
us to genetically examine wild rats derived from both Japan and
Germany. The genetic profiles obtained in this study were com-
pared, not only between the wild rats, but also among an additional
48 laboratory rat strains, for which data were taken from the
Whitehead Institute/Massachusetts Institute of Technology (WI/
MIT) rat database (WI/MIT 1998). The genetic relationships be-
tween the wild and the laboratory rats were calculated.
For this purpose, three male individuals from the Japanese wild
rat strains (partially inbred) Mitake B, C, and D (Kondo et al.
1996) and three individual male German wild rats (Klo¨ting et al.
1997) were chosen for examination. DNA was extracted from the
liver, and PCR reactions were performed by using fluorescein-
labeled primers. PCR products were separated by electrophoresis
on polyacrylamide gels and detected by a Shimadzu DSQ-500
DNA sequencer. The product lengths were determined with the aid
of a sequence ladder in combination with a control strain (WTC)
that had been previously listed in the WI/MIT database. In total, 42
microsatellite markers, two from each end of each autosome and
two from each end of Chr X, were analyzed. The markers were
chosen from the WI/MIT database and were selected for high
polymorphic rates and nucleotide differences of at least 3 bp
within the 48 laboratory strains.
The most surprising finding was the number of newly identi-
fied alleles. In about 80% of the examined loci, at least one allele
from the wild rats had never before been observed in any inbred
strain. Table 1 shows the distribution of the new alleles among the
wild rats. The number of new alleles derived from German rats is
greater than that of the Japanese wild rats. This is possibly due to
the different degrees of heterozygosity (Japanese rats 5–10%, Ger-
man rats 21–29%), which cannot be compared directly: the Japa-
nese wild rats were partially inbred strains (Ohno et al. 1994),
while the German rats were captured individually animals.
The average percentage of polymorphic loci between Japanese
and German wild rats is greater than 70% (cf. Table 2). This is at
the upper level of, yet in the same range as, the data that are
published for the inbred rat strains in the WI/MIT database. The
polymorphic rate within each group, the Japanese and the German,
was confirmed as described previously (Kondo et al. 1996; Klo¨ting
et al. 1997). The results for the German wild rats are slightly larger
owing to the more sensitive acrylamide-gel electrophoresis, in
comparison with the agarose-gel electrophoresis that was used in
the previous German wild-rat report (Klo¨ting et al. 1997). These
findings support the idea of a relatively independent genetic de-
velopment of the wild rats in Japan and Germany and reveal the
limited gene pool of the laboratory rat strains. Finally, we calcu-
lated the degree of relationship among all Japanese wild rats, all
German wild rats, and the 48 inbred strains from the WI/MIT
database, by means of hierarchical cluster analysis (SPSS Com-
puter Package). The “Between Groups Lilnkage” was used as the
clustering method, and “Squarred Euclidean Distance” served as
the measure. This type of clustering not only takes into account the
polymorphic rate, but also the different number of nucleotide bases
in the case of polymorphism. Six groups were defined in order to
describe the mathematical relationships between the laboratory
and the wild rats (cf. Fig. 1). The areas of these six groups are
Correspondence to: E-mail: Serikawa@scl.kyoto-u.ac.jp
Table 1. Percentage of markers that showed new alleles.
MITB MITC MITE HR2 G3 RU1
33 31 31 48 45 45
MITB, MITC, and MITE refer to Japanese Mitake strains B, C, and E; HR2, G3, and
RU1 indicate individual wild German rats.
Markers with new alleles: D1Rat3, D1Rat81, D2Rat189, D2Rat69, D3Rat144,
D4Rat7, D4Rat68, D5Rat121, D5Rat5, D6Rat3, D6Rat47, D8Rat68, D8Rat7,
D9Rat44, D9Rat100, D10Rat96, D10Rat6, D11Rat22, D11Rat46, D12Rat53,
D13Rat86, D14Rat10, D15Rat27, D16Rat12, D17Rat53, D18Rat112, D18Rat76,
D19Rat34, D19Rat59, D20Rat5, D20Rat55, DXRat8, DXRat101.
Table 2. Polymorphisms (%) between Japanese wild strains MITB, MITC, and
MITE and German wild rats HR2, G3, and RU1.
MITB MITC MITE HR2 G3 RU1
MITB 2 60 76 76 76
MITC 2 62 76 76 76
MITE 60 62 71 69 74
HR2 76 76 71 60 62
G3 76 76 69 60 50
RU1 76 76 74 62 50
© Springer-Verlag New York Inc. 2000Mammalian Genome 11, 789–790 (2000).