Male-sterile phenotype of the neurological mouse mutant weaver.

Abstract

The autosomal recessive murine mutation weaver (wv) affects postnatal differentiation in at least three neuronal populations in the brain: dopamine-containing neurons in the mid-brain, and granule and Purkinje cells in the cerebellum. Neuronal populations vulnerable to the actions of weaver die in the midst of development. In addition, homozygous weaver males are sterile. We show by a histological analysis of epididymides and testes that the cause of male sterility in weaver is lack of sperm. The epididymides of the adult weaver mice examined were devoid of sperm, and few seminiferous tubules in the adult weaver's testes contained elongated spermatids. Most tubules were marked by moderate to severe degeneration of the seminiferous epithelium. A developmental study showed that the mutant phenotype emerged after the third postnatal week. By postnatal day 28, the development of weaver sperm lagged behind that of the wild-type and some seminiferous tubules contained degenerating germ cells. By postnatal day 35, terminal differentiation of spermatids appeared to be arrested in many tubules and degeneration of the seminiferous epithelium was widespread. The heterozygotes were unaffected at all ages sampled. We conclude that the normal allele at the weaver locus is necessary for spermiogenesis and the maintenance of spermatogenesis.