Impact of genetic profiles on experimental studies: outbred versus wild rats

Abstract

Most rats used in toxicological or pharmacological research are obtained from outbred stocks. It is assumed that they are characterized by a high degree of genetic heterogeneity, reflecting that of the human population. However, most outbred stocks available have been kept as restricted colonies over a long period of time, decreasing their genetic variability. Since it is unclear to what extent genetic variability can be expected from an outbred stock, we analyzed 20 rats from each of two outbred stocks, Crl:WIST and Rj:SD, and compared them with 17 unrelated wild rats, using 90 randomly selected microsatellite markers, located on 20 autosomes and chromosome X. Up to 8 alleles per locus were found in wild rats compared with the maximum of 4 alleles in Crl:WIST and 3 alleles in Rj:SD rats. Therefore, significant differences were observed in the mean of number of alleles between Crl:WIST (2.3 ± 0.6) and Rj:SD (1.7 ± 0.6), as well as between both outbred stocks and wild rats (4.6 ± 1.5). The lowest heterozygosity was in Rj:SD (0.27 ± 0.19), which was significantly different from Crl: WIST (0.41 ± 0.19) and wild rats (0.35 ± 0.21). Our findings clearly show loss of alleles in both outbred stocks compared with wild rats and demonstrate that the designation “outbred stock” is no guarantee for genetic and phenotypic variability. This fact will have a significant impact on generation of new outbred stocks as well as performing multistrain experiments and thereby it may reduce false-positive and false-negative results in toxicological and pharmacological research in the future.