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A null mutation in inositol polyphosphate 4-phosphatase type I causes selective neuronal loss in weeble mutant mice.

Weeble mutant mice have severe locomotor instability and significant neuronal loss in the cerebellum and in the hippocampal CA1 field. Genetic mapping was used to localize the mutation to the gene encoding inositol polyphosphate 4-phosphatase type I (Inpp4a), where a single nucleotide deletion results in a likely null allele. The substrates of INPP4A are intermediates in a pathway affecting intracellular Ca(2+) release but are also involved in cell cycle regulation through binding the Akt protooncogene; dysfunction in either may account for the neuronal loss of weeble mice. Although other mutations in phosphoinositide enzymes are associated with synaptic defects without neuronal loss, weeble shows that Inpp4a is critical for the survival of a subset of neurons during postnatal development in mice.

Pubmed ID: 11683991


  • Nystuen A
  • Legare ME
  • Shultz LD
  • Frankel WN



Publication Data

October 25, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: CA20408
  • Agency: NCI NIH HHS, Id: CA34196
  • Agency: NINDS NIH HHS, Id: NS31348

Mesh Terms

  • Alleles
  • Animals
  • Apoptosis
  • Ataxia
  • Calbindins
  • Calcium
  • Cell Cycle
  • Cell Death
  • Cerebellum
  • Gene Deletion
  • Gene Expression
  • Hippocampus
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Motor Activity
  • Mutation
  • Neurons
  • Phosphoric Monoester Hydrolases
  • S100 Calcium Binding Protein G