Fine Mapping Of A Qtl Regulating The Onset Of Puberty On Chromosome X In Mice

Puberty,influenced by both environmental and genetic factors,is a complicated biologic process involving sexual maturation and gaining ability of reproduction.Onset of puberty is triggered by reactivation of the hypothalamic-pituitary-gonadal(HPG)axis and modulated by both genetic and environmental factors.Previous studies suggested that chromosome X could harbor gene(s)regulating the pubertal onset.We previously mapped a QTL in the age of vaginal opening to a～25 centimorgan(cM)interval(DXMit103～DXMit119,LOD=3.86)on chromosome X in mice.Here,we narrowed the QTL to a～2.5cM interval (DXMit68～RS29053133(50～60Mb))using interval-specific congenic strains(ISCS).Two inbred strains of mice,C3H/HeJ(C3H)and C57BL/6J(B6), which differed significantly in the puberty timing,were mated in reciprocal crosses to generate two pedigrees.Male F2 mice were genotyped and the individuals that held at least one recombination at the special interval(DXMit103～DXMit119)were chosen.The chosen male F2 mice backcross with female C3H to generate F3.The female F3 backcross with male C3H to generate F4.Genotyping was carried out again in male F4 mice and chosen the individuals that held only one recombination at the special interval to create ISCS.Thirteen ISCSs and one controlled strains were developed for fine mapping the QTL on puberty timing.The chosen male F4 backcross with female C3H to generate F5.And the age at VO of all female mice of F5 progenies was recorded.Data analysed using One-Way ANOVA by SPSS 15.0.The result suggested three candidated genes,including Pgrmcl,Gria3 and Plac 1,which may regulate the onset of puberty in mice.The findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty,and also reveal the fact that chromosome X(the sex chromosome)does carry gene(s)which take part in the regulative pathway of the puberty onset in mice.