The Mouse juvenile spermatogonial depletion (jsd) Phenotype Is Due to a Mutation in the X-Derived Retrogene, mUtp14b

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (32), p.11695-11700
• Main Authors: Rohozinski, Jan, Bishop, Colin E., Yanagimachi, Ryuzo
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; DNA Mutational Analysis; Evolution, Molecular; Exons; Gene Rearrangement; Genes; Genetic Diseases, X-Linked - genetics; Genetic mutation; Genetics; Germ cells; Infertility, Male - genetics; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Phenotype; Phenotypes; Phylogeny; Rats; Ribonucleic acid; Ribonucleoproteins, Small Nucleolar - genetics; RNA; Sequence Homology, Nucleic Acid; Spermatogenesis; Spermatogenesis - genetics; Spermatozoa; Testes; Testis; X Chromosome; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0401130101

The recessive juvenile spermatogonial depletion (jsd) mutation results in a single wave of spermatogenesis, followed by failure of type A spermatogonia to differentiate, resulting in adult male sterility. We have identified a jsd-specific rearrangement in the mouse homologue of the Saccharomyces cerevisiae gene UTP14, termed mUtp14b. Confirmation that mUtp14b underlies the jsd phenotype was obtained by transgenic bacterial artificial chromosome (BAC) rescue. We also identified a homologous gene on the Mus musculus X chromosome (MMUX) (mUtp14a) that is the strict homologue of the yeast gene, from which the intronless mUtp14b has been derived by retrotransposition. Expression analysis showed that mUtp14b is predominantly expressed in the germ line of the testis from zygotene through round spermatids, whereas mUtp14a, although well expressed in all somatic tissues, could be detected only in the germ line in round spermatids. In yeast, depletion of the UTP proteins impedes production of 18S rRNA, leading to cell death. We propose that the retroposed autosomal copy mUtp14b, having acquired a testis-specific expression pattern, could have provided a mechanism for increasing the efficiency and/or numbers of germ cells produced by meeting the need for more 18S rRNA and protein. Such a mechanism would be of obvious reproductive advantage and be strongly selected for in evolution. Consistent with this hypothesis is the finding of a similar X-autosome retroposition of UTP14 in human which seems to have arisen independently of that in rodents. In jsd homozygotes, which lack a functional copy of Utp14b, insufficient production of rRNA quickly leads to a cessation of spermatogenesis.