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A Quantitative Trait Locus on Chromosome 6 Regulates the Onset of Puberty in Mice

Division of Pediatric Endocrinology and Metabolism (B.M.N., M.R.P.), Rainbow Babies and Children’s Hospital, University Hospitals of Cleveland, and Departments of Pediatrics (B.M.N., C.A.H., P.J.S., M.R.P.) and Genetics (L.C.B., J.H.N., M.R.P.), Case School of Medicine, Cleveland, Ohio 44106

Address all correspondence and requests for reprints to: Mark R. Palmert, M.D., Ph.D., Division of Pediatric Endocrinology and Metabolism, Rainbow Babies and Children’s Hospital, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106. E-mail: mark.palmert{at}case.edu.

Puberty is a fundamental developmental process experienced by all reproductively competent adults, yet the specific factors that regulate variation in its timing remain elusive. Using a new approach to identifying these factors, we have performed a survey among a panel of chromosome substitution strains (for inbred strains C57BL/6J and A/J) followed by linkage analysis to map a quantitative trait locus (QTL) on the distal end of chromosome 6 that regulates pubertal timing (as assessed by vaginal opening) in mice. The location of the QTL was then refined to a region between marker D6MIT59 and the end of the chromosome by generating and phenotyping a panel of 12 congenic strains, each with a unique and overlapping homozygous segment of the A/J chromosome on an otherwise uniform C57BL/6J genomic background. Additional characterization of the QTL indicated that the effects of the responsible gene(s) are gender specific and inherited in a codominant manner without parent-of-origin effects. These findings represent an important advancement toward identification of novel factors that regulate maturation of the hypothalamic-pituitary-gonadal axis and determine the timing of puberty.

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