Quantitative trait loci analysis of mice administered the methionine–choline deficient dietary model of experimental steatohepatitis
Article first published online: 5 SEP 2006
Volume 26, Issue 8, pages 1000–1005, October 2006
How to Cite
Rangnekar, A. S., Lammert, F., Igolnikov, A. and Green, R. M. (2006), Quantitative trait loci analysis of mice administered the methionine–choline deficient dietary model of experimental steatohepatitis. Liver International, 26: 1000–1005. doi: 10.1111/j.1478-3231.2006.01314.x
- Issue published online: 5 SEP 2006
- Article first published online: 5 SEP 2006
- Received 15 March 2006,accepted 29 May 2006
Abstract: Background: Nonalcoholic steatohepatitis (NASH) is a common disease with a poorly understood etiology, and the methionine–choline-deficient (MCD) diet is a nutritional model of NASH. Quantitative trait loci (QTL) analysis is a standard method for chromosomal mapping of polygenic disease traits. The purpose of this study is to administer mice an MCD diet in order to determine the strain-specific susceptibility for developing steatohepatitis, and to apply a computational methodology of QTL analysis to identify associated chromosomal susceptibility loci.
Methods: Inbred mice were fed an MCD diet and alanine aminotransferase (ALT), hepatic triglycerides, liver weight, and weight loss were measured as phenotypic markers of steatohepatitis.
Results: A/J mice developed the highest ALT and hepatic triglyceride levels. Using linear regression analysis, gene loci affecting serum ALT levels were identified on four chromosomes, and four loci that affect liver weight were also identified. In contrast, no QTLs for hepatic triglycerides or body weight were identified. Of note, loci for ALT and liver weight co-localized to proximal segments of chromosomes 2 and 15, in regions previously identified as QTLs for liver fibrosis.
Conclusions: These data indicate that experimental steatohepatitis is a polygenic disease with genes determining ALT, liver weight, and liver fibrosis.