Mice homozygous for the motheaten spontaneous mutation (Ptpn6me) develop severe autoimmune disease. Characteristics include by granulocytic skin lesions, pneumonitis, impaired humoral and cell-mediated immune responses, decreased responses to T cell and B cell mitogens and deficient cytotoxic T cell and NK cell activity. B cells are LY-1+. Homozygous mutant mice also exhibit hyperimmunoglobulinemia, and express multiple autoantibodies. Macrophages show increased proliferative capacity. In addition to defects in the immune system, motheaten mice show classic symptoms of osteoporosis due to an increased number and activity of osteoclasts in the bone marrow. The lifespan of homozygous motheaten mice is approximately 3 weeks with death attributed to a autoimmune pneumonitis.
|Allele Synonym(s)||me; SHP-1 deficient|
|Gene Symbol and Name||Ptpn6, protein tyrosine phosphatase, non-receptor type 6|
|Strain of Origin||C57BL/6J|
|General Note|| |
Genbank ID for this mutation: S63764
|Molecular Note||A single nucleotide (C) deletion at coding nucleotide position 228 (g.chr6:124732398Gdel on build GRCm38) creates a cryptic splice site. This results in the deletion of a 101bp segment in the encoded transcript, and a frameshift in the encoded protein.|