Wg2b^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Wg2b^CAST/EiJ
• Name: weight gain in high growth mice 2b; CAST/EiJ
• MGI ID: MGI:3762234
• QTL: Wg2b Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Mutation: Undefined
• Mutation details: This allele confers decreased body weight at 6- and 9-weeks of age and decreased fat pad mass compared to C57BL/6J. (J:125711)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

2 anatomical structure(s)

Notes

Wg2b exhibits additive inheritance.

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

J:125711

Previously identified weight gain QTL Wg2 at 61 cM on mouse Chromosome 2 was further refined into four separate loci named Wg2a, Wg2b, Wg2c, and Wg2d by analysis of seven overlapping subcongenic lines derived from B6.CAST-(D2Mit329-D2Mit457). Wg2a, Wg2b,and Wg2c exhibit additive effects on body weight and/or fat pad mass, while Wg2d exhibits overdominance on fat pad mass. Body weight was recorded at 2, 3, 6, and 9 weeks of age. Fat pad weights were measured at sacrifice at 9 weeks of age.

Wg2a affects body weight and is located between D2Ucd15 (74.729 Mb) and D2Mit94 (79.976 Mb). Homozygosity for CAST/EiJ-derived alleles at Wg2a confers increased body weight at 6- and 9-weeks of age. This locus also shows suggestive linkage to all fat pads with CAST/EiJ-derived alleles conferring increased fat pad mass.

Wg2b maps to an interval flanked by D2Mit476 (86.245 Mb) and D2Mit420 (118.069 Mb). Homozygosity for CAST/EiJ-derived alleles at Wg2b confers decreased body weight at 6- and 9-weeks of age and decreasedfat pad mass for all fat pads. Wg5 (112 Mb) maps near this locus and the authors theorize it is likely identical to Wg2b.

Wg2c maps to an interval between D2Mit420 (118.069 Mb) and D2Mit107 (132.927 Mb). This locus is associated with fat pad mass. Homozygosity for CAST/EiJ-derived alleles at Wg2c confers increased retroperitoneal, gonadal, and total fat pad mass.

Heterozygosity for C57BL/6J- and CAST/EiJ-derived alleles at Wg2d confers decreased fat pad mass for all fat pads compared to either C57BL/6Jor CAST/EiJ homozygotes. Wg2d maps to an interval between D2Mit194 (143.623 Mb) and D2Mit196 (160.152 Mb).

J:135426

eQTLs associated with body weight in high growth mice were identified using microarray analysis. High growth strain C57BL/6J-Socs2^hg exhibits significantly increased growth trajectory after 3 weeks of age compared to CAST/EiJ. Previously constructed congenic lines B6.CAST-(D2Mit329-D2Mit457) and B6.CAST-(D2Mit329-D2Mit457) Socs2^hg carry CAST/Ei-derived chromosome 2 DNA from 75 Mb (45 cM) to 180 Mb (107 cM). This region contains weight gain QTL Wg2 located at 61 cM. The Wg2 locus is composed of multiple QTLs, Wg2a, Wg2b, Wg2c and Wg2d. Authors hypothesize coincident QTLs Wg2b (55 cM) and Wg5 (51 cM) are identical.

F2 intercrosses were constructed between C57BL/6J-Socs2^hg and B6.CAST-(D2Mit329-D2Mit457) Socs2^hg or wild type B6.CAST-(D2Mit329-D2Mit457). Whole brain RNA from F2 animals were screened by microarray assay to detect differential expression of genes located within the congenic interval. Significant eQTL identified include 2900064A13Rik (formerly AI451465), Scg5, Prei4 (formerly 2310032D16Rik), Trmt6 (formerly 3300001M20Rik) and Actr5.

Scg5 at 115 Mb (55.5 cM) is considered a high priority candidate gene for Wg2b/Wg5 due to expression correlation and colocalization. Scg5 expression is significantly upregulated in F2 animals homozygous for CAST/Ei-derived alleles at the congenic interval (LOD=16.4 at D2Mit207). In addition, Scg5 expression is up regulated in C57BL/6J-Socs2^hg high growth mice at various weeks of age (weeks 3, 4.5 and 9) compared to wild type C57BL/6J mice indicating Scg5 regulation isaltered by Socs2^hg status.

Scg5 mRNA expression was also examined in whole brain mRNA from BXD (B=C57BL/6J; D=DBA/2J) RI strains and CXB (C=BALB/cJ; B=C57BL/6J) RI strain. Scg5 expression levels correlated with body weight in both setsof RI strains.This eQTL accounts for over 75% of the Scg5 mRNA level variance observed in the 2 congenic crosses and 2 recombinant inbred crosses.

Sequence analysis of Scg5 detected 4 polymorphisms in the promoter region specific to high expressing strains BALB/cByJ,C3H/HeJ, DBA/2Jand CAST/EiJ. Furthermore, low expressing strain C57BL6J carries a unique haplotype block encompassing the Scg5 region as compared to high expressing strains C3H/HeJ, DBA/2J, BALB/cByJ and CAST/EiJ.

References

• Original: J:125711 Farber CR, et al., Dissection of a genetically complex cluster of growth and obesity QTLs on mouse chromosome 2 using subcongenic intercrosses. Mamm Genome. 2007 Sep;18(9):635-45
• All: 1 reference(s)