CHARACTERIZATION OF THE INBRED CE J MOUSE STRAIN AS AMYLOID RESISTANT/

Inbred CE/J mice have been identified as extremely resistant to azocas ein-induced amyloidosis relative to five commonly used inbred strains, A/J, CBA/J, C57BL/6J, C3H/HeN, and SJL/J. The enhanced amyloid resist ance in CE/J mice seems to derive from the novel structure of the SAA gene family in CE/J mice, as determined by Southern blot hybridization analysis of SAA gene structure and isoelectric focusing analysis of a cute phase SAA proteins in the six inbred strains. In CE/J mice, a sin gle, novel SAA isoform of pl 6.15 is present, whereas in the other str ains the amyloidogenic SAA2 isoform (pI 63) is codominantly expressed with SAA1 (pl 6 45). Two other inbred strains, PERU and IS/CAM, share common SAA specific HindIII DNA fragments with CE/J mice. Wild derived Mus musculus mice differ from all of the inbred strains studied, both in SAA gene structure and in the pattern of SAA isoform production; t wo isoforms, one pl 615 and the other pI 63 (corresponding to SAA2), w ere codominantly expressed. Only the pI 615 isoform, not SAA1 and 2, w as produced by CE/J mice in response to lipopolysaccharide, casein, si lver nitrate, interleukin-1, or tumor necrosis factor; tumor necrosis factor was a weaker stimulus than interleukin-1 for the pl 6.15 isofor m as it is for SAA1 and 2 production in the other inbred strains. This study provides a new line of evidence supporting the role of precurso r structure as a determining factor in murine amyloid A amyloidosis an d provides a valuable model for studies of amyloidogenesis.