کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245916 | 1209958 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
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چکیده انگلیسی
Background & Aims: Mice with a disrupted gene for the G-protein α inhibitory 2 chain (Gnai2â/â) develop a spontaneous colitis resembling human inflammatory bowel disease. Disease expression differs markedly between inbred strains of mice, indicating genetic control of disease susceptibility. We performed a genome-wide screen to localize the chromosomal regions regulating disease expression. Methods: A total of 284 F2 mice derived from resistant C57BL/6J Gnai2â/â mice and susceptible C3H/HeN Gnai2â/â mice were analyzed in a genome-wide screen for colitis susceptibility and severity. Results: A highly significant locus on chromosome 3 (Gpdc1) contributed to colitis susceptibility and severity (likelihood ratio statistics [LRS] = 32.4; LOD score = 7; P < 1.0 à 10â5). The peak linkage of this locus at 62 cM colocalizes exactly with a previously identified locus controlling colitis susceptibility in interleukin-10-deficient mice. In addition, evidence for linkage with a locus on chromosome 1 (Gpdc2; LRS = 19.7; LOD = 4.3) was found, and the 2 loci interacted epistatically (combined LRS = 68.2). A third locus (Gpdc3) was found on chromosome 9 and this locus interacted epistatically with a locus on chromosome 7, which by itself did not have an effect on the trait. Conclusions: The identification of a major locus on chromosome 3 that controls susceptibility to spontaneous colitis in 2 different gene-knockout models indicates that this locus harbors a gene(s) that plays a key role in maintaining mucosal homeostasis. Identification of this gene(s) may contribute to further understanding of the mechanisms underlying human inflammatory bowel disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 128, Issue 1, January 2005, Pages 74-85
Journal: Gastroenterology - Volume 128, Issue 1, January 2005, Pages 74-85
نویسندگان
Michelle E.A. Borm, Jianping He, Brian Kelsall, A. Salvador Peña, Warren Strober, Gerd Bouma,