Lprq4^NZB/BlNJ
QTL Variant Detail

Summary

• QTL variant: Lprq4^NZB/BlNJ
• Name: lipoprotein QTL 4; NZB/BlNJ
• MGI ID: MGI:3511886
• QTL: Lprq4 Location: Chr5:114021753-129632606 bp Genetic Position: Chr5, Syntenic

Variant origin

• Strain of Specimen: NZB/BlNJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased total cholesterol on a CHOW diet and increased HDL cholesterol on CHOW and atherogenic diets compared to SM/J. (J:29072)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Lprq4 exhibits additive inheritance and has a stronger effect in females compared to males.

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

J:29072

Linkage analysis was performed on 184 (NZB/BlNJ x SM/J)F2 animals to identify QTLs associated with lipoprotein metabolism on CHOW and atherogenic diets. 125 polymorphic loci at an average spacing of 20 cM were used in the genome scan.

On a CHOW diet, parental strain NZB/BlNJ exhibits 2.5-fold greater total plasma cholesterol compared to parental strain SM/J. Triglycerides and free fatty acids were comparable between the 2 parental strains on the CHOW diet. On a 5-week atherogenic diet, parental strain SM/J exhibits decreased HDL cholesterol and significantly increased LDL and VLDL cholesterol compared to NZB/BlNJ. Triglycerides and free fatty acids were comparable between the 2 parental strains on the atherogenic diet.

A locus near D1Mit36 (92.3 cM) on mouse Chromosome 1 shows linkage to total cholesterol (LOD=5.9), HDL cholesterol (LOD=6.9), and plasma Apoa2 levels (LOD=14.8) on a CHOW diet. D1Mit36 also shows linkage to plasma Apoa2 levels on an atherogenic diet (LOD=7.9). This locus is named Lprq3 (lipoprotein QTL 3). The Apoa2 gene (92.6 cM) colocalizes with Lprq3 and shows significant linkage to total cholesterol on a CHOW diet (LOD=6.6) and HDL cholesterol on a CHOW (LOD=8.1) and atherogenic diet (LOD=3.6). NZB/BlNJ-derived alleles confer increased HDL cholesterol and plasma Apoa2 levels on CHOW and atherogenic diets. Lprq3 appears to exhibit additive inheritance. Sequence analysis of Apoa2 cDNA revealed 2 nonconservative polymorphisms between NZB/BlNJ and SM/J.

An interval on mouse Chromosome 5 between 61 cM (D5Mit25) and 72 cM (D5Mit30) shows linkage to total cholesterol (LOD=6.7) and HDL cholesterol (LOD=5.3) on a CHOW diet and HDL cholesterol (LOD=5.6) on an atherogenic diet. This locus is named Lprq4. Lprq4 shows a stronger effect in female animals compared to male animals. NZB/BlNJ-derived alleles confer increased total cholesterol (CHOW) and HDL cholesterol (CHOW and atherogenic) at Lprq4. This QTL appears to exhibit additive inheritance.

A locus on mouse Chromosome 7 near D7Mit55 (15 cM) shows linkage to total plasma triglycerides (LOD=5.1) and free fatty acids (LOD=5.6) on an atherogenic diet. This locus is named Lprq5. Candidate genes mapping near Lprq5 are Lipe (5.5 cM), Apoe (4 cM), Apoc2 (4 cM), and Apoc1 (4 cM).

References

• Original: J:29072 Purcell-Huynh DA, et al., Genetic factors in lipoprotein metabolism. Analysis of a genetic cross between inbred mouse strains NZB/BINJ and SM/J using a complete linkage map approach. J Clin Invest. 1995 Oct;96(4):1845-58
• All: 1 reference(s)