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Proc Natl Acad Sci U S A 2008 Feb 19;105(7):2349-53. Epub 2008 Feb

Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis.

Bhandari, R; Juluri, KR; Resnick, AC; Snyder, SH.

Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

Inositol pyrophosphates, also designated inositol diphosphates, possess high-energy beta-phosphates that can pyrophosphorylate proteins and regulate various cellular processes. They are formed by a family of inositol hexakisphosphate kinases (IP6Ks). We have created mice with a targeted deletion of IP6K1 in which production of inositol pyrophosphates is markedly diminished. Defects in the mutants indicate important roles for IP6K1 and inositol pyrophosphates in several physiological functions. Male mutant mice are sterile with defects in spermiogenesis. Mutant mice are smaller than wild-type despite normal food intake. The mutants display markedly lower circulating insulin.

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