Abnormal gonad development in Kit^W-2Bao mice caused by a Kit gene missense mutation

• Published in: Chinese science bulletin 2010-12, Vol.55 (36), p.4143-4149
• Main Authors: Wu, BaoJin, Yin, LiJing, Lu, ZhengLan, Yin, YuShu, Yang, WeiWei, Yang, Rong, Kang, XiaoDong, Liu, GuiJie, Yin, HongPing, Yu, LiPing, Gu, MeiEr, Wu, PeiLin
• Format: Article
• Language: English
• Subjects: 单基因; 原始生殖细胞; 工具包; 杂合子缺乏; 突变小鼠; 结构异常
• ISSN: 1001-6538; 1861-9541
• DOI: 10.1007/s11434-010-4219-8

Kit^W-2Bao mice are single-gene autosomal dominant mutation mice with a B6 background that were bred in our laboratory. Heterozygotes had morphological characteristics including albinism of the abdomen, extremities, and tail, whereas the homozygotes had albinism of the body, black eyes, and infertility. The homozygous mutants showed small, structurally abnormal gonads, and lacked germ cells. Heterozygous male mice lacked germ cells in some contorted seminiferous tubules. This mutation has been mapped at 43.8 cM from the centromere in chromosome 5 by linkage analysis and Kit has been identified as the candidate gene. After Kit full-length mRNA amplification, it was found that a G to T conversion at position 1228 in the ORF changed the 410th amino acid from V to F. This amino acid change could affect the protein＇s secondary structure. Heterozygous mutant mice were intercrossed and homozygous mutant mice were bred and genotyped. We found that no primordial germ cells （PGCs） appeared in the urogenital ridge area at fetus day 11.5 in the homozygotes. The number of PGCs also significantly decreased in heterozygotes. At fetus day 15.5, the differentiation of the testis tubule structure was unclear; as well, they contained no spermatogonia. Female homozygotes contained no primordial follicles in the ovary. The numbers of PGCs and primordial follicles were significantly decreased in heterozygous mice. W^2Bao is the only mutated site in the extracellular 4th Ig-like domain and this mutant mouse model provides new material for the study of the mechanism of reproductive system development.