A Kinase-Dead Allele of Lyn Attenuates Autoimmune Disease Normally Associated with Lyn Deficiency
Anne M Verhagen, Morgan E Wallace, Ankita Goradia, Sarah A Jones, Hayley A Croom, Donald Metcalf, Janelle E Collinge, Mhairi J Maxwell, Margaret L Hibbs, Warren S Alexander, Douglas J Hilton, Benjamin T Kile, Robyn Starr
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2009
Lyn kinase, a member of the Src family of tyrosine kinases, functions as both a positive and negative regulator of B cell activation. In the absence of Lyn, BCR signaling is unregulated, leading to perturbed B cell development, hyperactive B cells, and lethal Ab-mediated autoimmune disease. We have generated a mutant mouse pedigree, termed Mld4, harboring a novel mutation in the gene encoding Lyn, which renders the protein devoid of kinase activity. Despite similarities between the phenotypes of Lyn(Mld4/Mld4) and Lyn(-/-) mice, the spectrum of defects in Lyn(Mld4/Mld4) mice is less severe. In particular, although defects in the B cell compartment are similar, splenomegaly, myeloid expansion..View full abstract
Awarded by Australian National Health and Medical Research Council
This work was supported by Program Grant 461219 and fellowships (to M.J.M.. M.L.H.. W.S.A., and D.J.H.) from the Australian National Health and Medical Research Council, fellowships from the Australian Research Council (to B.T.K.), the Cancer Council of Victoria (to D.M.), and the Sylvia and Charles Viertel Foundation (to R.S.). This study was supported in part by research funding from MuriGen Pty Ltd.