Protection of murine lupus by the Ead transgene is MHC haplotype-dependent.

Protection of Murine Lupus by the Ea Transgene Is MHC Haplotype-Dependent

Role of the major histocompatibility complex class II Ea gene in lupus susceptibility in mice.

The gene(s) encoded within major histocompatibility complex (MHC) act as one of the major genetic elements contributing to the susceptibility of murine systemic lupus erythematosus (SLE). We have recently demonstrated that lupus susceptibility is more closely linked to the I-E- H-2(b) haplotype than to the I-E+ H-2(d) haplotype in lupus-prone BXSB and (NZB x BXSB)F1 hybrid mice. To investigate ...

Protection of murine systemic lupus by the Ea transgene without expression of I-E heterodimers.

A high-level expression of the Ea transgene encoding the MHC class II I-E alpha-chain is very effective in the protection from systemic lupus erythematosus (SLE) in mice. However, it has not been elucidated whether this protection results from the induction or increased expression of I-E heterodimers or from the generation of I-E alpha-chain-derived peptides displaying high affinity for I-A mol...

The Yaa gene abrogates the major histocompatibility complex association of murine lupus in (NZB x BXSB)F1 hybrid mice.

To investigate the specific contribution of select MHC class II genes on the development of murine lupus, H-2 congenic (NZB x BXSB)F1 hybrid mice bearing either H-2b/b, H-2d/b, or H-2d/d haplotypes were generated. We compared the clinical development (autoantibody production and glomerulonephritis) of systemic lupus erythematosus (SLE) in these three F1 hybrids in the presence or absence of the...

Far upstream regions of class II MHC Ea are necessary for position-independent, copy-dependent expression of Ea transgene.

The chromatin upstream of the class II MHC Ea gene contains specific, DNase I hypersensitive (DH) sites (groups I-V), overlapping and extending the promoter proximal and distal control regions. To determine whether the Ea DH groups I-V define a functionally important chromatin domain or locus control region (LCR), we have used wild type Ead gene constructs to generate transgenic mouse lines fro...