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Sertoli Cell Vacuolization and Abnormal Germ Cell Adhesion in Mice Deficient in an Inositol Polyphosphate 5-Phosphatase¹

^a Genetic Diseases Research Branch, National Human Genome Research Institute, ^b Veterinary Resources Program, Office of Director, National Institutes of Health, Bethesda, Maryland 20892

The dynamic nature of cellular interactions during differentiation of germ cells and their translocation from the basement membrane to the lumen of the seminiferous tubules requires the existence of complex and well-regulated cellular adhesion mechanisms in the testis. Successful migration of the developing germ cells is characterized by dynamic breakage and reformation of cadherin-containing adherens junctions between the germ cells and Sertoli cells, the polarized somatic cells of the testis that support and nourish the developing gametes. Here, we demonstrate the accumulation of abnormally swollen, actin-coated, endosome-like structures that contain intact adherens junctions and stain positive for N-cadherin and ß-catenin in the Sertoli cell cytosol of mice deficient in Inpp5b, an inositol polyphosphate 5-phosphatase. Simultaneous to the formation of these abnormal structures, developing germ cells are prematurely released from the seminiferous epithelium and sloughed into the epididymis. Our results demonstrate a role for Inpp5b in the regulation of cell adhesion in the testis and in the formation of junctional complexes with neighboring cells, and they emphasize the important and essential role of phosphoinositides in spermatogenesis.

First decision: 24 October 2001.

¹ Supported by Division of Intramural Research, National Human Genome Research Institute.

² Correspondence: Robert L. Nussbaum, Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, Building 49, Room 4A72, Bethesda, MD 20892-4472. FAX: 301 402 2170; rlnuss{at}nhgri.nih.gov

³ Current address: CuraGen Corporation, 322 East Main Street, Branford, CT 06405

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