A Dominant X-Linked QTL Regulating Pubertal Timing In Mice Found By Finemapping

Puberty,often influenced by both enviromental 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 axis(HPGA) and modulated by both genetic and environmental factors.Previou studies suggested that chromosomeXcould habor gene(s) regulating the pubertal onset.We previously mapped a QTL in the age of vaginal opening to a～2.5 centimorgan(cM) interval(DXMit225-DXMit140) of mouse chromosomeX.Here,we narrowed the QTL to a～1cM (1.6Mb) interval by modified interval-specific congenic strain(mISCS) analysis.Previous work in our lab was that we performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ(C3H) and C57BL6/J(B6),which differed significantly in the pubertal timing,Vaginal opening(VO) was used to characterize pubertal timing in female mice(two parental strains,F1 and F2 progeny) was recorded.A genome-wide search was performed in phenotypically extreme F2 female mice out of progeny of the F1 intercrosses to identify quantitative trait loci(QTLs) controlling this trait.A QTL significantly associated was mapped to～25cM (DXMit103～DXMit119,LOD=3.86).The location of the significant QTL on ChrX was then fine-mapped to a region of～2.5cM between marker DXMit225 and DXMit140.In this study,Male mice held B6 genes in the DXMit225～DXMit140 interval were chosen by genotyping and continued to backcross with C3H for three times to F7.The age at VO, first cornification,and onset of cyclicity of all female mice(F7 progeny) was recorded,and the antral diameter of follicles from 26-day-old female mice(F7 progeny) was meaured,genotyping was carried again in male mice(F6 progeny) to create mISCS.Eight of mISCS were developed and one controlled strains+(The genotype of F7 female mice is X~CX~C in the special interval) for finemapping the QTL on puberty timing.Data analysed by One-Way ANOVA and the result advised ten genes were underling one which regulate the onset of puberty.Such 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 pubertal timing in mice.