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An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity.

Cell | Dec 22, 2000

http://www.ncbi.nlm.nih.gov/pubmed/11163182

A model has been proposed for the regulation of CD45, and by homology other RPTPs, in which dimerization inhibits phosphatase activity through symmetrical interactions between an inhibitory structural wedge and the catalytic site. Here, we report the phenotype of mice with a single point mutation, glutamate 613 to arginine, that inactivates the inhibitory wedge of CD45. The CD45 E613R mutation causes polyclonal lymphocyte activation leading to lymphoproliferation and severe autoimmune nephritis with autoantibody production, resulting in death. Both homozygotes and heterozygotes develop pathology, indicating genetic dominance of CD45 E613R. The dramatic phenotype of CD45 E613R mice demonstrates the in vivo importance of negative regulation of CD45 by dimerization, supporting the model for regulation of CD45, and RPTPs in general.

Pubmed ID: 11163182 RIS Download

Mesh terms: Animals | Antigens, CD45 | Autoimmunity | B-Lymphocytes | Cell Division | Dimerization | Gene Expression | Heterozygote | Homozygote | Immunoglobulin A | Interleukin-10 | Lupus Nephritis | Lymphocyte Activation | Mice | Mice, Inbred C57BL | Mice, Mutant Strains | Phenotype | Point Mutation | Proteinuria | Renal Insufficiency | Survival Rate | T-Lymphocytes | Transcription, Genetic

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01-GM39553

Mouse Genome Informatics (Data, Gene Annotation)

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