title: Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: a step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function.
abstract: Homozygosity for the motheaten (me) or viable motheaten (mev) mutations causes severe dysregulation of murine hematopoiesis with the consequent development of both immunodeficiency and systemic autoimmunity. Expression of this phenotype has now been linked to loss-of-function mutations in the gene encoding PTP1C, an intracellular tyrosine phosphatase predominantly expressed in cells of hemopoietic origin. As discussed in this article, the association of PTP1C mutation with the multiple hemopoietic defects found in motheaten mice indicates that this tyrosine phosphatase is critical to normal hematopoiesis and is consistent with the recognized importance of protein tyrosine phosphorylation in modulating the cell signaling pathways governing proliferation and differentiation. The motheaten mouse therefore provides a powerful model of delineating the precise function of PTP1C and thereby elucidating the specific molecular mechanisms whereby this tyrosine phosphatase participates in the control of hemopoietic cell differentiation and function.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Bignon
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D017027:Protein Tyrosine Phosphatases