Sequence of i‐e genes from autoimmune new zealand white mice

Abstract

Autoimmune New Zealand white (NZW) mice contribute to (New Zealand black × New Zealand white)F1 mice 1 or more major histocompatibility complex‐linked genes that strongly correlate with susceptibility to murine lupus. The NZW class II major histocompatibility complex genes, I‐Eα and I‐Eβ, were cloned and sequenced and found to differ from normal B10.PL (H‐2u) mice by 3 amino acids in the first domain of the I‐Eβ subunit. Of these differences, the arginine at position 72 of NZW mice could be an important disease determinant since it lies in a predicted antigen‐binding cleft.

Contributions ofEazandEbzMHC Genes to Lupus Susceptibility in New Zealand Mice

“…the New Zealand model of lupus (13,14,38,39). Our results, however, indicate that lupus-like disease in this model is not influenced by Ea z and/or Eb z genes.…”

“…The present studies were designed to determine whether Ea z and/or Eb z genes account for the genetic contribution of H2 z to lupus-like disease in New Zealand hybrid mice. Previous studies have shown that the ␤1 exon sequences of these genes are identical with those reported for Ea u and Eb u genes (14,(37)(38)(39)(40)(41). Based on various sequence homologies, it was predicted that these class II molecules would enhance the production of pathogenic IgG autoantibodies in FIGURE 3.…”

A genetic analysis of lupus

“…Heterozygosity at Lbw1 (H‐2 d/z ) conferred the greatest susceptibility than either H‐2 d or H‐2 z haplotypes consistent with previous studies (10, 11). NZB (H‐2 d ) and NZW (H‐2 z ) class II genes (12–16), the NZW TNF‐α gene (9, 17), or both (8) have been suggested as candidates for this locus. Recently, a recessively transmitted NZW locus, designated Sles1 , that also mapped to the MHC region was suggested to act as an epistatic modifier that suppressed autoimmune disease in the NZW strain (18).…”