Basic-alimentary tractLinkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn’s disease
Section snippets
Animals
SAMP1/Yit mice1 have been propagated as a specific pathogen-free colony for more than 20 generations under protocols approved by the Institutional Animal Care and Use Committee following American Association of Accreditation of Laboratory Animal Care guidelines. We now distinguish this line from the original strain as SAMP1/YitFc.4 AKR/J (AKR) mice were purchased from The Jackson Laboratory (Bar Harbor, ME). Female AKR and (AKR × SAMP1/Fc)F1 mice bred to male SAMP1/Fc mice produced F1 and
Histologic analysis suggests a dominant protective effect at a single locus by AKR alleles
Ileitis of variable severity is found in nearly all SAMP1/Fc mice after 10 weeks of age (total inflammatory score: median, 11.25; range, 1.5–16.5; n = 16), and the lesions persist throughout the remaining life of the mice.1, 2, 3, 4 In contrast, AKR mice display little evidence of inflammation (range of total inflammatory scores, .25–1.5 by 30 weeks of age; n = 4), even after sharing cages with SAMP1/Fc mice for >3 months before examination. Similarly, we found little evidence of inflammation
Discussion
We have shown that allelic differences in Pparg can regulate expression of an underlying genetic susceptibility to Crohn’s-like ileitis in mice. We also have shown that minor allelic variants of PPARG are associated strongly with disease resistance in humans. Other groups have proposed that PPARγ plays a role in susceptibility to inflammatory bowel disease in humans (reviewed in Daynes and Jones16), and we now show positive evidence for association with Crohn’s disease. PPARG maps to 3(p25–p26)
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Supported by the National Institute of Digestive, Diabetes, and Kidney Diseases (PO1 DK57880), the Crohn’s and Colitis Foundation (to K.S.), and the Uehara Memorial Foundation (to K.K.).