Two kinds of ENU-induced scant hair mice and mapping of the mutant genes.

OBJECTIVE: To establish mouse models for human diseases through N-ethyl-N-nitrosourea (ENU) mutagenesis, and to provide groundwork to clone genes and study their functions after mapping the mutant genes. METHODS: 18 male D2 mice (G0) at age of 8-10 weeks old were injected intraperitoneally with ENU (100 mg/kg) once a week for three consecutive weeks. The treated male mice were mated with females of the same strain, and their offspring (G1) were used to screen for dominant and recessive mutation. After breeding the mutant F2 (D2B6 F1 intercrossing) mice, 39 microsatellites that are equally distributed on the mouse genome and are different between B6 and D2 strains were used to scan the genome. According to the log odds score (LODS) we determined whether these microsatellites were linked to the mutant genes and calculated the location of mutant genes based on their recombination ratio. RESULTS: We screened 532 G1 mice, of which 14 exhibited mutation phenotypes. None was dominantly hereditable. Two cases of recessive inheritable scant hair mice were obtained through testing 30 G1 mice with normal phenotype and potential recessive mutant genes. All showed scant coat hair, grew slowly, and hyperkeratoses of epidermis and bollicular horn plug in histological sections. Their visceral organs were not markedly different from normal, and they were named scant hair 1 Baojin (symbol is snthr(-1Bao)) and scant hair 2 Baojin (symbol is snthr(-2Bao)). Through microsatellite screening we found that the LODS between snthr(-1Bao) and D9Mit243 was 7.73, and the linkage was determined. After analyzing the recombination ratio between snthr(-1Bao) and microsatellite D9Mit18 which was near snthr(-1Bao) based on a total number of 126 F2 mice with the scant hair phenotype, we determined that snthr(-1Bao) was located at chromosome 9 and was 71cM from centromere. Using the same technique, snthr(-2Bao) was mapped to the same position as snthr(-1Bao). CONCLUSION: In our research, two cases of scant hair mice provide good models for the study of dermatology, and the location of mutant genes provides a solid foundation for cloning new mice scant hair genes.