Fl2sa^A/JNshm
QTL Variant Detail

Summary

• QTL variant: Fl2sa^A/JNshm
• Name: fatty liver 2 in SMXA; A/J
• MGI ID: MGI:3723479
• QTL: Fl2sa Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: A/JNshm

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased liver total lipid content and increased liver weight compared to SM/JNshm. (J:124974)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:124974

Linkage 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 12^SM/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.

References

• Original: J:124974 Kumazawa M, et al., Searching for genetic factors of fatty liver in SMXA-5 mice by quantitative trait loci analysis under a high-fat diet. J Lipid Res. 2007 Sep;48(9):2039-46
• All: 1 reference(s)