Cq3^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Cq3^C57BL/6J
• Name: cholesterol QTL 3; C57BL/6J
• MGI ID: MGI:2155364
• QTL: Cq3 Location: Chr3:101888918-101889067 bp Genetic Position: Chr3, cM position of peak correlated region/allele: 44.3 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased plasma total cholesterol compared to KK. (J:108417)
• Inheritance: Not Specified

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Cq3 interacts with Cq2 on mouse Chromosome 1. (C57BL/6J x KK-A^y)F2 animals homozygous for C57BL/6J-derived alleles at Cq3 and homozygous for KK-derived alleles at Cq2 have significantly increased plasma total cholesterol compared to other genotypes.

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

J:54322

95 microsatellite markers at an average density of 14.4-16.5 cM were used to map loci affecting obesity-associated plasma lipid concentrations in 190 (C57BL/6J x KK-Ay)F2 animals. KK-Ay animals develop severe obesity and elevated plasma lipid concentrations while C57BL/6J remain lean with lower lipid levels. F2 animals of genotype a/a at the agouti locus have an intermediate plasma cholesterol phenotype while F2 animals of genotype Ay/a have a plasma cholesterol phenotype resembling the KK-Ay parental strain.

Three QTLs involved in plasma cholesterol concentrations were identified: Cq1 (LOD = 4.6) and Cq2 (LOD = 5) are linked to D1Mit425 and D1Mit150, respectively, on mouse chromosome 1, and Cq3 (LOD = 4.3) is linked to D3Mit102 on chromosome 3.

Cq2 in linkage with D1Mit150 maps to within 1.1 cM of the Apoa2 locus. Sequencing of Apoa2 cDNA in C57BL/6J and KK revealed 7 nucleotide substitutions (resulting in 3 amino acid substitutions) within the open reading frame.

Nq1 (LOD = 4.3), a QTL involved in plasma NEFA (non-esterified fatty acids) concentrations, mapped to chromosome 9 in association with D9Mit353.

J:108417

Previously identified cholesterol QTL Cq3 on mouse Chromosome 3 was further refined by mapping 93 female a/a animals from a (C57BL/6J x KK-A^y)F2 intercross. The peak LOD score for plasma free cholesterol mapped to 49.7 cM near D3Mit102 (LOD=4.5). Suggestive linkage to plasma total cholesterol, HDL cholesterol, LDL cholesterol, and phospholipids also occurs at this locus. The 95% confidence interval of Cq3 spans 47 cM - 54 cM between D3Mit29 and D3Mit102.

Linkage of D3Mit102 to cholesterol traits was also examined in several other mouse crosses: (KK x RR)F2, (C57BL/6J x RR)F2, and (KK x CF1)F2. Cq3 was not detected in any of these populations.

Previously identified cholesterol QTL mapping near Cq3 on mouse Chromosome 3 include Hdl35 (28 cM), Tchol1 (49.2 cM), Hdl5 (33 cM), and Hdlq21 (56 cM).

A significant interaction was detected between Cq3 and Cq2 on distal mouse Chromosome 1 near D1Mit150. Cq2 is thought to be Apoa2 so the interaction between Cq3 and Apoa2/Cq2 was analyzed in 190 F2 animals. Itwas found that F2 animals homozygous for C57BL/6J-derived alleles at Cq3 and homozygous for KK-derived alleles at Apoa2/Cq2 exhibited the highest plasma total cholesterol values compared to all other genotypes.

Apoa1bp is proposed as a possible candidate gene for Cq3. No differences between C57BL/6J and KK Apo1bp sequences were discovered, however Apo1bp is known to interact with Apoa2.

References

• Original: J:54322 Suto J, et al., Quantitative trait loci that regulate plasma lipid concentration in hereditary obese KK and KK-Ay mice. Biochim Biophys Acta. 1999 Mar 30;1453(3):385-95
• All: 2 reference(s)