کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245586 | 1209949 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn's disease
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کلمات کلیدی
NF-κBQTLPPARNuclear factor κ B - عامل هسته ای κ Bquantitative trait locus - علامت کمی صفتpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازSingle-nucleotide polymorphism - پلی مورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتیدperoxisome proliferator-activated receptor - گیرنده فعال فعال پروکسیوم
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn's disease Linkage to peroxisome proliferator-activated receptor-γ in SAMP1/YitFc mice and in human Crohn's disease](/preview/png/9245586.png)
چکیده انگلیسی
Background & Aims: Genetic predisposition is implicated strongly in Crohn's disease. Disease-associated mutations in NOD2/CARD15, the best-studied susceptibility gene in this disorder, explain only a small fraction of the heritability. The SAMP1/YitFc (SAMP1/Fc) mouse strain expresses many features of Crohn's disease in humans. We bred SAMP1/Fc to disease-resistant AKR mice to identify additional susceptibility genes that may play a role in human disease. Methods: Linkage disequilibrium mapping was performed in an (AKR à SAMP1/Fc) backcross to SAMP1/Fc, followed by sequencing, expression analysis using reverse transcription polymerase chain reaction (PCR) and immunohistochemistry, and functional testing in vivo of the regional candidate gene encoding the peroxisome proliferator-activated receptor γ (Pparg). A cohort-based association study was performed in humans. Results: We show that ileitis is blocked in SAMP1/Fc mice by inheritance of AKR alleles on chromosome 6 in the region of Pparg. Major differences in Pparγ expression in the parental mouse strains are found specifically in the crypts of the small intestine, and treatment of ileitis-prone mice with a Pparγ agonist decreased disease severity in susceptible mice expressing low levels of the protein. Rare alleles of PPARG are associated significantly with Crohn's disease in humans. Conclusions: We have identified Pparg as a susceptibility gene in both the SAMP/Yit mouse and in human Crohn's disease. Similarities between Crohn's disease and the SAMP1/Fc model suggest that the effect of this gene in humans may be mediated through regulation of PPARγ activity in the crypts of the small intestine.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 128, Issue 2, February 2005, Pages 351-360
Journal: Gastroenterology - Volume 128, Issue 2, February 2005, Pages 351-360
نویسندگان
Kazuhiko Sugawara, Timothy S. Olson, Christopher A. Moskaluk, Brian K. Stevens, Sharon Hoang, Kosuke Kozaiwa, Fabio Cominelli, Klaus F. Ley, Marcia McDuffie,