Searching for genetic factors of fatty liver in SMXA-5 mice by quantitative trait loci analysis under a high-fat diet

Mayumi Kumazawa, Misato Kobayashi, Fusayo Io, Takahiro Kawai, Masahiko Nishimura, Tamio Ohno, and Fumihiko Horio

Graduate school of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601

Corresponding Author: horiof{at}agr.nagoya-u.ac.jp

Fatty liver is strongly associated with metabolic syndrome such as obesity, insulin resistance, and type 2 diabetes, but the genetic basis and functional mechanisms linking fatty liver with metabolic syndrome are largely unknown. The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterized by moderately impaired glucose tolerance, hyperinsulinemia, and mild obesity. SMXA-5 mice also developed fatty liver, and a high-fat diet markedly worsened this trait, although SM/J and A/J are resistant to fatty liver development under a high-fat diet. To dissect loci for fatty liver in the A/J regions of the SMXA-5 genome, we attempted quantitative trait loci (QTL) analysis in (SM/J × SMXA-5)F2 intercross mice fed a high-fat diet. We mapped a major QTL for relative liver weight and liver lipid content near D12Mit270 on chromosome 12, and designated this QTL Fl1sa. The A/J allele at this locus contributes to the increase in these traits. We confirmed the effect of Fl1sa on lipid accumulation in liver by using the A/J-Chr12^SM consomic strain showed significantly less accumulation than A/J mice. This suggests that the SM/J and A/J strains, neither of which develops fatty liver, possess loci causing for fatty liver, and that the coexistence of these loci causes fatty liver in SMXA-5 mice.

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