20 Sex Chromosomes, Sexual Development, and Sex Reversal in the Dog

Abstract

Canine reproductive biology has many features that are species-specific; however, prenatal development of the canine reproductive system follows the same steps observed in other mammals. The molecular aspects of canine developmental biology can now be studied in detail, being accelerated by recent advances in canine genomics, such as the 7.6× canine genomic sequence, and the integrated radiation hybrid map and linkage map of all chromosomes, including the sex chromosomes. This chapter outlines the molecular pathways controlling the three major steps in sexual development, summarizing studies in several mammals. Sections discussing abnormalities in sexual development identify those reported in the dog. An example summarized in some detail is sex reversal, a disorder for which the dog may be a particularly useful model. Although transgenic mouse models have been useful in defining mammalian sexual development, differences in gene expression patterns have been observed between mice and other mammals, including humans. Thus, the dog could be a more representative molecular model for comparative studies of mammalian sexual development that will benefit both dogs and humans.

OVERVIEW OF SEX DETERMINATION IN MAMMALS
Normal mammalian sexual development occurs in three steps, with each step depending on successful completion of the previous step: (1) establishment of chromosomal sex complement at the time of fertilization, (2) development of gonadal sex, wherein either a testis or ovary emerges from the bipotential gonad, and (3) development of phenotypic sex by differentiation of either male or female internal and external genitalia (Fig. 1). At fertilization, normal canine zygotes obtain either...