Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice

Si Tse Jiang, Yuan Yow Chiou, Ellian Wang, Hsiu Kuan Lin, Sue Ping Lee, Hsin Yi Lu, Chi Kuang Leo Wang, Ming Jer Tang, Hung Li

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


Juvenile nephronophthisis type I is the most common genetic disorder causing end-stage renal failure in children and young adults. The defective gene responsible has been identified as NPHP1. Its gene product, nephrocystin-1, is a novel protein of uncertain function that is widely expressed in many tissues and not just confined to the kidney. To gain insight into the physiological function of nephrocystin, Nphp1- targeted mutant mice were generated by homologous recombination. Interestingly, homozygous Nphp1 mutant mice were viable without renal manifestations of nephronophthisis. They appeared normal, but males were infertile with oligoteratozoospermia. Histological analysis of the seminiferous tubules showed that spermatogenesis was blocked at the early stages of spermatid elongation, with degenerating spermatids sloughing off into the lumen. Electron microscopic analysis revealed detachment of early elongating spermatids from Sertoli cells, and a failure of sperm head and tail morphogenesis. However, a few mature spermatozoa were still deposited in the epididymis, though they were frequently dead, immotile, or malformed. These novel findings indicate that nephrocystin is critically required for the differentiation of early elongating spermatids into spermatozoa in mice. The possible roles of nephrocystin in the formation and maintenance of Sertoli - spermatid junctions are still under investigation.

Original languageEnglish
Pages (from-to)3368-3379
Number of pages12
JournalHuman Molecular Genetics
Issue number21
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Targeted disruption of Nphp1 causes male infertility due to defects in the later steps of sperm morphogenesis in mice'. Together they form a unique fingerprint.

Cite this