• PMID: 21078623
• Gene Name: NPHP4
• Condition: Male mutants are sterile and show reduced sperm motility and epididymal sperm counts
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male mutants are sterile and show reduced sperm motility and epididymal sperm counts

NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development

Won J, Marín de Evsikova C, Smith RS, Hicks WL, Edwards MM, Longo-Guess C, Li T, Naggert JK, Nishina PM.

Nephronophthisis (NPHP) is an autosomal recessive kidney disease that is often associated with vision and/or brain defects. To date, 11 genes are known to cause NPHP. The gene products, while structurally unrelated, all localize to cilia or centrosomes. Although mouse models of NPHP are available for 9 of the 11 genes, none has been described for nephronophthisis 4 (Nphp4). Here we report a novel, chemically induced mutant, nmf192, that bears a nonsense mutation in exon 4 of Nphp4. Homozygous mutant Nphp4(nmf192/nmf192) mice do not exhibit renal defects, phenotypes observed in human patients bearing mutations in NPHP4, but they do develop severe photoreceptor degeneration and extinguished rod and cone ERG responses by 9 weeks of age. Photoreceptor outer segments (OS) fail to develop properly, and some OS markers mislocalize to the inner segments and outer nuclear layer in the Nphp4(nmf192/nmf192) mutant retina. Despite NPHP4 localization to the transition zone in the connecting cilia (CC), the CC appear to be normal in structure and ciliary transport function is partially retained. Likewise, synaptic ribbons develop normally but then rapidly degenerate by P14. Finally, Nphp4(nmf192/nmf192) male mutants are sterile and show reduced sperm motility and epididymal sperm counts. Although Nphp4(nmf192/nmf192) mice fail to recapitulate the kidney phenotype of NPHP, they will provide a valuable tool to further elucidate how NPHP4 functions in the retina and male reproductive organs. FAU - Won, Jungyeon AU - Won J AD - The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. FAU - Marín de Evsikova, Caralina AU - Marín de Evsikova C FAU - Smith, Richard S AU - Smith RS FAU - Hicks, Wanda L AU - Hicks WL FAU - Edwards, Malia M AU - Edwards MM FAU - Longo-Guess, Chantal AU - Longo-Guess C FAU - Li, Tiansen AU - Li T FAU - Naggert, Jürgen K AU - Naggert JK