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

作　　者：WU BaoJin YIN LiJing LU ZhengLan YIN YuShu YANG WeiWei YANG Rong KANG XiaoDong LIU GuiJie YIN HongPing YU LiPing Gu MeiEr WU PeiLin 

机构地区：[1]Laboratory of Experimental Animal Science, Hangzhou Normal University, Hangzhou 310036, China [2]Comparative Medicine Centre of Yangzhou University, Yangzhou 225000, China

出　　处：《Chinese Science Bulletin》2010年第36期4143-4149,共7页

基　　金：supported by the National Natural Science Foundation of China (30670231);the Zhejiang Science and Technology Project for Laboratory Animal (2009F80022)

摘　　要：KitW-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.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.

关 键 词：突变小鼠 结构异常 单基因 套件 性腺 原始生殖细胞 工具包 杂合子缺乏 

分 类 号：Q954[生物学—动物学] TM262[一般工业技术—材料科学与工程]