Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase

Monita P. Wilson, Christopher Hugge, Malgorzata Bielinska, Peter Nicholas, Philip W. Majerus, David B. Wilson

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Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a key regulatory enzyme at the branch point for the synthesis of inositol hexakisphosphate (IP6), an intracellular signaling molecule implicated in the regulation of ion channels, endocytosis, exocytosis, transcription, DNA repair, and RNA export from the nucleus. IP6 also has been shown to be an integral structural component of several proteins. We have generated a mouse strain harboring a β-galactosidase (βgal) gene trap cassette in the second intron of the Itpk1 gene. Animals homozygous for this gene trap are viable, fertile, and produce less ITPK1 protein than wild-type and heterozygous animals. Thus, the gene trap represents a hypomorphic rather than a null allele. Using a combination of immunohistochemistry, in situ hybridization, and βgal staining of mice heterozygous for the hypomorphic allele, we found high expression of Itpk1 in the developing central and peripheral nervous systems and in the paraxial mesoderm. Examination of embryos resulting from homozygous matings uncovered neural tube defects (NTDs) in some animals and axial skeletal defects or growth retardation in others. On a C57BL/6 x 129(P2)Ola background, 12% of midgestation embryos had spina bifida and/or exencephaly, whereas wild-type animals of the same genetic background had no NTDs. We conclude that ITPK1 is required for proper development of the neural tube and axial mesoderm.

Original languageEnglish
Pages (from-to)9831-9835
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 16 2009


  • Exencephaly
  • Hypomorphic allele
  • Inositol signaling
  • Spina bifida


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