Amyloid resistance in A/J mice is determined by a single gene

Abstract

WIDESPREAD tissue deposition of the unique fibrous protein amyloid occurs in a variety of human diseases¹. ‘Secondary’ amyloidosis arises as a complication of chronic infectious or inflammatory disease and an identical syndrome can be induced in mice by repeated injections of casein². Little genetic work has been done in this area, probably because development of amyloidosis is often variable, even with a standard induction regimen, and results are inconsistent³. Furthermore, because of the many complex immunological aberrations occurring during the amyloid induction period⁴, the various experimental manipulaions which can affect it⁴, and the wide range of induction times seen in different murine strains², on would expect that multiple genes and alleles would influence amyloidogenesis. Nevertheless, the discovery of the uniquely resistant A strain⁵ suggested the posiblity of isolating at least part of the genetic analysis of amyloid induction in two inbred strains, CBA/J and A/J, differing markedly in susceptibility to amyloidosis⁵. We show for the first time that a single gene confers resistance on the A/J strain. Our results imply that genetic factors may also define subpopulations of chronic disease patients who are at greater risk from amyloid disease.