• PMID: 21561988
• Gene Name: RANBP9
• Condition: Essential for mouse spermatogenesis and oogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Essential for mouse spermatogenesis and oogenesis

RanBPM is essential for mouse spermatogenesis and oogenesis

Puverel S, Barrick C, Dolci S, Coppola V, Tessarollo L.

RanBPM is a recently identified scaffold protein that links and modulates interactions between cell surface receptors and their intracellular signaling pathways. RanBPM has been shown to interact with a variety of functionally unrelated proteins; however, its function remains unclear. Here, we show that RanBPM is essential for normal gonad development as both male and female RanBPM(-/-) mice are sterile. In the mutant testis there was a marked decrease in spermatogonia proliferation during postnatal development. Strikingly, the first wave of spermatogenesis was totally compromised, as seminiferous tubules of homozygous mutant animals were devoid of post-meiotic germ cells. We determined that spermatogenesis was arrested around the late pachytene-diplotene stages of prophase I; surprisingly, without any obvious defect in chromosome synapsis. Interestingly, RanBPM deletion led to a remarkably quick disappearance of all germ cell types at around one month of age, suggesting that spermatogonia stem cells are also affected by the mutation. Moreover, in chimeric mice generated with RanBPM(-/-) embryonic stem cells all mutant germ cells disappeared by 3 weeks of age suggesting that RanBPM is acting in a cell-autonomous way in germ cells. RanBPM homozygous mutant females displayed a premature ovarian failure due to a depletion of the germ cell pool at the end of prophase I, as in males. Taken together, our results highlight a crucial role for RanBPM in mammalian gametogenesis in both genders. FAU - Puverel, Sandrine AU - Puverel S AD - Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, NCI, Frederick, MD 21702, USA. FAU - Barrick, Colleen AU - Barrick C FAU - Dolci, Susanna AU - Dolci S FAU - Coppola, Vincenzo AU - Coppola V