title: B and T cells are not required for the viable motheaten phenotype.
abstract: Hematopoietic cell phosphatase (HCP), encoded by the hcph gene, (also called PTP1C, SHP, SH-PTP1, and PTPN6) is deficient in motheaten (me/me), and the allelic viable motheaten (me(v)/me(v)) mice. Since HCP is expressed in many cell types and protein phosphorylation is a major mechanism of regulating protein function, it is not surprising that the motheaten phenotype is pleiotropic. It is commonly thought that immune system involvement causes this disease. If so, the motheaten disease ought to be alleviated when the recombination activation gene-1 (RAG-1) is disrupted because there will be no V(D)J rearrangement and thus impaired development of B and T cells. We bred homozygous, double-mutant me(v)/me(v) x RAG 1 -/- mice and found that, in fact, inflamed paws, and splenomegaly with elevated myelopoiesis. Thus, except for autoantibodies, the motheaten phenotype does not depend on the presence of B and T cells. This observation cautions the use of motheaten mice as a model of autoimmune disease.
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada.
authors.forename: C C
authors.initials: CC
authors.lastname: Yu
authors.forename: H W
authors.initials: HW
authors.lastname: Tsui
authors.forename: B Y
authors.initials: BY
authors.lastname: Ngan
authors.forename: M J
authors.initials: MJ
authors.lastname: Shulman
authors.forename: G E
authors.initials: GE
authors.lastname: Wu
authors.forename: F W
authors.initials: FW
authors.lastname: Tsui
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D001402:B-Lymphocytes; D003872:Dermatitis / Q000473:pathology; D004195:Disease Models, Animal; D005838:Genotype; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000473:pathology; D008214:Lymphocytes; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis; D013601:T-Lymphocytes
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C064658:RAG-1 protein; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse