Journal article

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

Abstract

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..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

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.