Interactions of the Scid or Beige Mutations with the Viable Motheaten Mutation

Abstract

The viable motheaten (me^v) mice are characterized by a moth-eaten appearance of the coat, immunodeficiency, autoimmunity, generalized inflammatory disease, paws necroses, and early death. The target of the single point me^v mutation is PTP1C, a protein tyrosine phosphatase whose deficient expression in hematopoietic cells should explain all phenotypic features of me^v mice, particularly their autoimmune and inflammatory pathologies. In order to evaluate their role in the development of the me^v mouse disease, we constructed me^vscid congenics to probe the impact of autoimmunity and me^vbeige congenics to probe the impact of elastase and cathepsine G neutrophil activities. Both me^vscid and me^vbeige mice were nearly equivalent to me^v mice with regards to moth-eaten appearance, paw necroses and early death. Thus, autoimmunity does neither initiate nor substantially enhance the me^v mouse syndrome. Moreover, the beige mutation-linked deficiency of protease activity of neutrophils is unable to significantly reduce the me^v mutation-dependent inflammatory pathology.

Key Words:

• viable motheaten mouse
• beige mouse
• scid mouse
• PTP1C
• deficiency