Gene Mutation in Mice Produces Disease Similar to Human SLE

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Gene Mutation in Mice Produces Disease Similar to

Human SLE

WESTPORT, CT (Reuters Health) Jan 29 - In a murine

model, mutation of a gene that codes for alpha-

mannosidase II, an enzyme involved in N-glycan

production, produces a systemic autoimmune disease

similar to systemic lupus erythematosus (SLE) seen in

humans, according to a report published in the January

30th issue of the Proceedings of the National Academy of

Sciences.

Dr. Jamey D. Marth from the University of California San

Diego in La Jolla and colleagues studied mice with a

mutation in the alpha-mannosidase II gene and found

that although lymphocyte development, abundance, and

activation parameters were normal, serum

immunoglobulins were elevated and a progressive lupus-

like kidney dysfunction occurred.

The researchers also found that the gene mutation led to

autoantibody reactivity and circulating immune

complexes. In addition, anti-nuclear antibodies were

formed that demonstrated reactivity toward histone, Sm

antigen, and DNA.

" By whatever means, the loss of alpha-mannosidase II

alters N-glycan branching and clearly attenuates the

immune system's ability to maintain self-tolerance, " the

investigators explain.

" This is an entirely new manner by which autoimmune

disease can occur, by a gene controlling carbohydrate

formation, " Dr. Marth stated in a UCSD news release.

" These findings provide new insights into understanding

autoimmune disease and suggest new diagnostic tests

for possible causes of human SLE. "

Proc Natl Acad Sci USA 2001;98:1142-1147.