Wg5^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Wg5^CAST/EiJ
• Name: weight gain in high growth mice 5; CAST/EiJ
• MGI ID: MGI:3698755
• QTL: Wg5 Location: unknown Genetic Position: Chr2, cM position of peak correlated region/allele: 56.9 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

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 compared to C57BL/6J. This allele is associated with increased Scg5 brain mRNA expression compared to A/J. (J:117545, J:135426)

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: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:117545 Farber CR, et al., Fine mapping reveals sex bias in quantitative trait Loci affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11. Genetics. 2007 Jan;175(1):349-60
• All: 2 reference(s)