lupus mice

[Guest guest]

> Especially

> interesting is that lupus can be installed in normal inbred mice using

> just 2 of the genes from the NZB/NZW inbred mouse model complex. So

> these things are not always intractably polygenic.

Here's an illustration of what I mean. There's a lot of loci that have

been studied in lupus mice; some of these are probably from knockout

models and others from inbred ones:

" Thus far, linkage analyses in multiple murine models have detected 31

susceptibility loci distributed among 21 nonoverlapping genomic

intervals, clearly illustrating the complexity of the genetic basis

for susceptibility to systemic autoimmunity (2). "

Sounds terribly complex. But - you can play some damn effective games

using just a handful of them:

" By combining the Sle1, Sle2, and Sle3 loci into a triple congenic

strain, we have shown that these loci contain the minimal set of genes

sufficient to reconstitute a fully penetrant SLE pathogenesis (16).

[...] we have identified a series of NZW-derived negative epistatic

modifiers of Sle1. The most potent one, Sles1, specifically turns off

all of the Sle1 immune phenotypes, leading to the suppression of the

entire autoimmune pathological process triggered by Sle1 interactions

with other Sle loci (19). "