Pubertal Phenotype In Interval-Specific Congenic Mouse Strains

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. Generally, when human growth and development get to a certain period, With the hypothalamic-pituitary-gonadal axis (HPGA) mature, to start the development of the adolescent. However, the exact molecular mechanism is not clear.Recently, Many people take advantage of the mice to study the mechanism of the puberty. In2004, PaLmert used chromosome substitution strains(CSSs) technology to study the puberty of female mice mechanism. they evaluated pubertal timing [as assessed by vaginal opening (VO)] in two inbred strains of mice, A/J and C57BL/6J(B6), and in a panel of chromosome substitution strains (CSSs) generated from A/J and B6mice. The results show that CSSs for chromosomes6and13each displayed significantly earlier time of VO than B6mice. but CSSs for chromosome X is not displayed significantly differences. In2006,Thomas used previous work that PaLmert performed a survey among a panel of chromosome substitution strains followed by link-age analysis to map a quantitative trait locus (QTL) on the distal end of chromosome6that regulates pubertal timing (asassessed by vaginal opening) in mice. The location of the QTL was then refined to a region between marker D6MIT59(60-75cM) and the end of the chromosome. In2008, 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 B6, which differed significantly in the pubertal timing, We previously mapped a QTL in the age of vaginal opening to a-2.5centimorgan (cM) interval (DXMit68-rs29053133) of mouse chromosome X. The use of the above experimental results, we have analyzed A/J, C3H and B6mice in the DNA sequence within the section of the X chromosome DXMit68-rs29053133. We found that the A/J and C3H have homologous about96%, whereas80%of the sequence is inconsistent with B6. Whether the chromosomal sequence differences between A/J and C3H mice do influence the pubertal phenotype significantly? In this study, Male mice held C3H genes in the DXMit68-rs29053133interval were chosen by genotyping and continued to backcross with C3H for four times to F6. The age at VO, ovarian morphology, growth curve of all female mice (F6progeny) was recorded.To determine whether the sequence differences between the two tains influence this phenotype. In addition, we analysed by mouse genome-wide scan chip interval-specific congenic mouse strains the background of degree of purification.and further located by11SNP loci. Here, we narrowed the QTL (ChrX:9129480-ChrX:69503547). Ultimately we excluded a (chrX:54036185to chrX:5672927), b (chrX:57726106) and c (chrX:59808608to chrX:5993923) in the three candidate genes,They are:Fh11, Gpr112, Fgf13.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.