Bodwt1^C3H/HeJ
QTL Variant Detail

Summary

• QTL variant: Bodwt1^C3H/HeJ
• Name: body weight 1; C3H/HeJ
• MGI ID: MGI:3624644
• QTL: Bodwt1 Location: unknown Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C3H/HeJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers increased plasma HDL cholesterol, LDL/VLDL cholesterol, triglycerides, and body weight compared to C57BL/6J. (J:106521, J:108422)
• Inheritance: Dominant

Expression

In Structures Affected by this Mutation:

2 anatomical structure(s)

Notes

This allele confers increased LDL/VLDL cholesterol with a codominant mode of inheritance.

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

J:108422

Loci linked to body weight, serum amyloid P (SAP), and hyperglycemia were mapped using 234 female animals from a (C57BL/6J-Apoe^tm1Unc x C3H/HeJ-Apoe^tm1Unc)F2 intercross. 134 polymorphic markers at an average resolution of 12 cM were used for the genome scan. Parental strain C3H/HeJ-Apoe^tm1Unc exhibit significantly increased body weight and plasma total cholesterol, HDL, and triglycerides, and slightly higher plasma glucose and insulin, compared to parental strain C57BL/6J-Apoe^tm1Unc.

A locus at95.8 cM (D1Mit206) on mouse Chromosome 1 named Bglu3 (blood glucose level 3) showed significant linkage to body weight (LOD=8.3), plasma glucose levels (LOD=4.1), and SAP (LOD=9.2). The Bglu3 support interval (SI) spans approximately 86 cM - 104 cM. C3H/HeJ-derived alleles at Bglu3 confer increased body weight and plasma glucose levels with a dominant mode of inheritance, and increased SAP with an additive mode of inheritance. Bglu3 explains 22% of the variance in glucose levels, 34% of the variance in body weight, and 66% of the variance in SAP. Apoa2 (92.6 cM) and Apcs (formerly Sap, 94.2 cM) map to the Bglu3 interval and are considered potential candidates. Previously identified body weight QTL Bw8q1 (100 cM) maps near Bglu3.

A second locus on mouse Chromosome 1 shows significant linkage to body weight at 81.6 cM (LOD=9 near D1Mit425). This locus explains 40% of the variance and is named Bodwt1 (body weight 1). The support interval for Bodwt1 spans 72 cM - 87 cM. C3H/HeJ-derived alleles at Bodwt1 confer increased body weight with a dominant mode of inheritance. A previously identified body weight QTL named Bw17 (69 cM) maps near this locus. A potential candidate gene mapping near Bodwt1 is Myog at 72.3 cM.

Significant linkage to body weight mapped to29.4 cM on mouse Chromosome 17 near D17Mit180 (LOD=3.4). This locus explains 7% of the variance and is named Bodwt2 (body weight 2). The support interval for Bodwt2 spans 19 cM - 35 cM. C3H/HeJ-derived alleles at Bodwt2 confer increased body weight with adominant mode of inheritance. A previously identified body weight QTL named Wt3q3 maps near this locus. Pla2g7 is a potential candidate gene for Bodwt2.

Suggestive loci for bodyweight mapped to 46 cM on mouse Chromosome 4 (LOD=2.7 at D4Mit153) and 54 cMon mouse Chromosome 14 (LOD=2.2 at D14Mit185). Suggestive linkage to plasma insulin mapped to 33 cM on mouse Chromosome 9 (LOD=2.7 at D9Mit207). Suggestive linkage to plasma glucose mapped to 38 cM on mouse Chromosome 9 (LOD=2.3 at D9Mit260).

J:106521

Linkage analysis was performed on 234 female animals from a (C57BL/6J-Apoe^tm1Unc x C3H/HeJ-Apoe^tm1Unc)F2 intercross to identify QTLs associated with atherosclerotic lesion size, plasma lipids, and body weight. Animals were place on a Western diet at 6 weeks of age for a duration of 12 weeks. On a Western diet, parental strain C3H/HeJ-Apoa^tm1Unc exhibits 6-fold increased plasma HDL cholesterol and 10-fold increased aortic lesion size compared to parental strain C57BL/6J. 130 polymorphic markers at an average spacing of 13 cM were used for the genome scan.

Significant linkage to plasma lipids and body weight mapped to 2 peaks on distal mouse Chromosome 1. These 2 linkages are collectively named Bodwt1 (body weight 1). Marker D1Mit425 at 81.6 cM is linked to plasma LDL/VLDL cholesterol (LOD=5.7), triglycerides (LOD=2.5), and body weight (LOD=9). Marker D1Mit270 at 92.3 cM is linked to plasma LDL/VLDL cholesterol (LOD=6.3), HDL cholesterol (LOD=3), and triglycerides (LOD=3.8). C3H/HeJ-derived alleles at Bodwt1 confer increased HDL cholesterol, triglycerides, and body weight with dominant inheritance, and increased LDL/VLDL cholesterol with codominant inheritance. Previously identified QTL Bw17 (75 cM), Bw8q1 (100 cM), Cq2 (100 cM), and Hdlq15 (104 cM)map near this locus. Apoa2 (92.6 cM) and Soat1 (81.6 cM) are potential candidate genes for Bodwt1.

Significant linkage to atherosclerotic lesion size mapped to a broad region of mouse Chromosome 9. This QTL is named Ath29 (atherosclerosis 29). Three peaks are detected within Ath29 at D9Mit206 (20 cM, LOD=2.9, 11% of variance), D9Mit360 (35 cM, LOD=3.7, 24% of variance), and D9Mit156 (42 cM, LOD=4.1, 34% of variance). C57BL/6J-derived alleles at Ath29 confer increased atherosclerotic lesion size with dominant inheritance, while C3H/HeJ-derived alleles confer smaller lesion size with recessive inheritance.

Significant linkage to body weight mapped to 29.8 cM on mouse Chromosome 17 near D17Mit180 (LOD=3.4). This locus is named Bodwt2 (body weight 2). C57BL/6J-derived alleles at Bodwt2 confer increased body weight with recessive inheritance. Previously identified body weight QTL Wt3q3 (14 cM) maps near this locus.

Suggestive linkage to atherosclerotic lesion size mapped to 20 cM on mouse Chromosome 11 near D11Mit236 (LOD=2.4). This locus explains 5% of the variance. C3H/HeJ-derived alleles at D11Mit236 confer decreased atherosclerotic lesion size with a dominant mode of inheritance.

Suggestive linkage to plasma LDL/VLDL cholesterol mapped to 68 cM on mouse Chromosome 5 near D5Mit95 (LOD=2.2) and 56 cM on mouse Chromosome 9 near D9Mit15 (LOD=2.5).

Suggestive linkage to plasma HDL cholesterol mapped to 58.8 cM on mouse Chromosome 3 near D3Mit42 (LOD=2.3).

Suggestive linkage to triglycerides mapped to 41 cM on mouse Chromosome 8 near D8Mit41 (LOD=3.2). Previously identified triglyceride QTLs Tgl1 (51.5 cM) and Trigq2 (30 cM) map near this locus.

Suggestive linkage to body weight mapped to 66 cM on mouse Chromosome 4 near D4Mit251 (LOD=2.7). This locusoverlaps with Bw7 at 59 cM. Suggestive linkage to body weight also mapped to 54 cM on mouse Chromosome 14 near D14Mit185 (LOD=2.2). This locus overlaps with Bwnd2wk7 at 52 cM.

J:127711

Linkage analysis was performed on 135 CHOW-fed females from a (B6.129P2-Apoe^tm1Unc/J x C3.129P2-Apoe^tm1Unc/Lus)F2 intercross to identify QTLs associated with atherosclerosis resistance/susceptibility. This same cross was previously used to identify athersclerosis QTLs on a Western-fed diet. Inbred strain C3H/HeJ is resistant to atherosclerosis compared to C57BL/6J. Animals were sacrificed at 12 weeks of age and genome scan was performed using genetic markers at a 10 cM resolution.

Significant linkage to HDL (LOD=7.1) and triglycerides (LOD=4.4) mapped to 92 cM on mouse Chromosome 1 near D1Mit540. This locus is likely identical to previously identified QTL Bodwt1. Potential candidate genes for Bodwt1 include Apoa2 (92.6 cM) and Soat1 (81.6 cM).

Ath4 on mouse Chromosome 4 was identified in this study at 28 cM with suggestive significance near D4Mit327 (LOD=2.6). C57BL/6J-derived alleles at Ath4 confer atherosclerosis susceptibility. A potential candidate gene for Ath4 is Angptl3 (48 cM). Tlr4 was previously considered a candidate for Ath4 but authors excluded this gene based on congenic line analysis. Replacing the defective C3H/HeJ allele of Tlr4 with a functional allele from C3H/DNA did not result in increased atherosclerosis susceptibility.

Significant linkage to atherosclerosis susceptibility mapped to 27 cM on mouse Chromosome 9 with LOD=5 near D9Mit25. This locus is believed to be identical to Ath29, which was previously identified in a BXH Western-fed population. C57BL/6J-derived alleles atAth29 confer atherosclerosis susceptibility in (B6.129P2-Apoe^tmiUnc/J x C3.129P2-Apoe^tm1Unc/Lus)F2 females. The Ath29 95% confidence interval spans 17 cM - 33 cM. Ath29 was confirmed in a congenic line carrying a C3H/HeJ-derived DNA segment from D9Mit297 (15 cM) to D9Mit16 (61 cM) on a B6.129P-Apoe^tm1Unc susceptible background. As expected congenic animals displayed decreased aortic lesion size compared to B6.129P2-Apoe^tm1Unc control animals. Potential candidate genes for Ath29 include Acat1 (30cM), Apoa1 (27 cM), Apoa4 (27 cM), Apoc3 (27 cM), Apoa5, Il10ra (26 cM), Il18 (29 cM), Nnmt (29 cM), Tirap (17 cM), Sorl1 (24 cM), Pafah1b2 (26 cM), Thsd4 (33 cM), and Loxl1 (33 cM).

Suggestive linkage to HDL (LOD=3.8) and triglycerides (LOD=2.5) mappedto14 cM on mouse Chromosome 10. Suggestive linkage to atherosclerosis susceptibility mapped to 58 cM (LOD=2.5).

References

• Original: J:108422 Su Z, et al., Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice. Hum Mol Genet. 2006 May 15;15(10):1650-8
• All: 3 reference(s)