Summary |
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Variant origin |
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Variant description |
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Phenotypes |
View phenotypes and curated references for all genotypes (concatenated display).
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Expression |
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Notes |
Candidate Genes
The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was previously identified in a SM/J SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is the fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-Chr 12SM/J consomic mice. [J:124974]. Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disease caused by interactions between environmental and genetic factors. Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, the authors had previously performed QTL analysis, using (SM/JSMXA-5)F2 intercross mice, and identified Fl1sa on Chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver. Mapping and Phenotype information for this QTL, its variants and associated markersJ:124974Linkage analysis was performed on 255 (SM/JNshm x SMXA-5/Nshm)F2 animals to identify genetic loci associated with fatty liver. Parental strain SMXA-5/Nshm is a recombinant inbred strain derived from SM/J and A/J. This strain exhibits moderately impaired glucose tolerance, mild obesity, and hyperinsulinemia. SMXA-5/Nshm also displays fatty liver on a short term high-fat diet. Progenitor strains SM/J and A/J are resistant to diet-induced fatty liver. F2 animals were placed on a high-fat diet for 7 weeks before phenotype analysis. A panel of 73 polymorphic markers was used for the genome scan. A QTL designated Fl1sa (fatty liver 1 in SMXA) showed significant linkage to relative liver weight. This locus maps to 13 cM on mouse Chromosome 12 near D12Mit270 (LOD=8.8). Fl1sa explains 15% of the phenotypic variance and also exhibits significant linkage to liver total lipid content (LOD=7.7) and liver triglyceride content (LOD=3.7). A/J-derived alleles at Fl1sa confers increased liver weight, liver total lipids, and liver triglycerides. Fl1sa was confirmed in a consomic line (A/J-Chr 12SM/J/Nshm) carrying the entire chromosome 12 derived from SM/J on an A/J genetic background. This line displays decreased liver weight, decreased liver total lipids and decreasedliver triglycerides as would be expected from SM/J-derived Fl1sa alleles. Lpin1 at 9 cM is a potential candidate gene for Fl1sa. A QTL designated Fl2sa (fatty liver 2 in SMXA) showed significant linkage to liver total lipid concentration (LOD=4.1) and relative liverweight (LOD=3.9). This locus maps to mouse Chromosome 2 between D2Mit162 (51.4 cM) and D2Mit28 (78.2 cM). Homozygosity for A/J-derived alleles at Fl2sa confer increased liver lipids and liver weight compared to homozygosity for SM/JNshm-derived alleles. Linkage to relative liver weight (LOD=2.5), total lipid content (LOD=2.7), and total cholesterol content (LOD=3.7) mapped to mouse Chromosome 17 between D17Mit29 (15.1 cM) and D17Mit68 (24.5 cM). Homozygosity for A/J-derived alleles at D17Mit29 confers increased liver total cholesterol content compared to SM/JNshm homozygotes. Suggestive linkage to liver total cholesterol mapped to 32 cM on mouse Chromosome 2 near D2Mit156 (LOD=2.5). SM/JNshm-derived alleles confer increased liver cholesterol at this locus. Suggestive linkage to liver triglyceride contentmapped to 96 cM near D2Mit226 (LOD=2.1) with the heterozygous genotype conferring increased liver triglycerides compared to either A/J or SM/JNshm homozygous genotypes.Suggestive linkage to liver total lipid concentration (LOD=2.1) and serum triglyceride concentration (LOD=2.4) mapped to 0.5 cM on mouse Chromosome 6 near D6Mit86.Suggestive linkage to serum triglyceride concentration mapped to 56 cM on mouse Chromosome 8 near D8Mit166 (LOD=2).Suggestive linkage to liver triglyceride content mapped to 35 cM on mouse Chromosome 10 near D10Mit15 (LOD=1.9).Suggestive linkage to liver weight (LOD=2.1) and serum triglyceride content (LOD=2.1) mapped to 40 cM on mouse Chromosome 11 near D11Mit15. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 12/10/2024 MGI 6.24 |
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