Igfbp3q2^DU6i
QTL Variant Detail

Summary

• QTL variant: Igfbp3q2^DU6i
• Name: insulin-like growth factor binding protein 3 QTL 2; DU6i
• MGI ID: MGI:2157863
• QTL: Igfbp3q2 Location: unknown Genetic Position: Chr10, Syntenic

Variant origin

• Strain of Specimen: DU6i

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased serum IGFBP-3 levels compared to DBA/2. (J:68837)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

Igfbp3q2 exhibits additive inheritance.

Candidate Genes

J:91835

The correlation between gene expression and dietary interaction was examined in a population of (BALB/cStCrlfC3H/Nctr x VY/WffC3Hf/Nctr-A(vy)/a)F1 animals. A/a and A/A^vy animals were placed on a 70% (calorie restricted) or 100% (non-restricted) diet andliver mRNA levels were assessed for over 18,000 genes using DNA microarrays. Twenty-eight known genes showing statistically significant differential expression between the 70% and 100% calorie diets and A/a and A/A^vy genotypes mapped near known diabesity QTLs. These genes may be considered further for candidate genes.

On mouse Chromosome 10, candidate genes for diabesity QTL Igfp3q2 (46 cM) are Aes (43 cM) and Hsp90b1 (49 cM). Aes shows differential expression between A/a and A/A^vy animals on both the restricted and unrestricted diets while Hsp90b1 shows differential expression between the restricted and unrestricted diets on the A/A^vy background. At another locus, Mdm2 (66 cM) is a candidate gene for diabesity QTL Insq4 (59 cM). Mdm2 shows differential expression between the restricted and unrestricted diets on the A/a background.

J:99477

Authors used novel data mining tool ExQuest to identify novel candidate genes for existing diabesity QTLs. Next, candidate gene expression in the liver, adipose, and pancreas of diabesity-prone Tally Ho mice and diabesity-resistant C57BL/6J mice was assessed by quantitative PCR analysis. Several potential candidate genes, some with no previous association to diabesity QTLs, were identified. Since QTL intervals may be large and could contain hundreds or thousands of potential candidate genes, this method allows researchers to focus on those with strong potential as well as identify novel candidate genes.

Potential candidate genes for Bgeq8 (57 cM) on mouse Chromosome 10 as identified by ExQuest are Rdh7 and Hsd17b9. Hsd17b9 exhibits 9.5-fold increased expression in the liver of Tally Ho compared to C57BL/6J animals. For QTLs Insq9 (44 cM) and Igfbp3q2 (46 cM), potential candidate genes Ass1 (20 cM Chr 2)), Ftcd, Col18a1 (41.3 cM), Itgb2 (41.5 cM), Agpat3 (41.8 cM), Ndufs7, Oaz1 (43 cM), Pah (47 cM), Igf1 (48 cM), Nr1h4 (50 cM), and Kitl (57 cM) were identified.

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

J:68837

411 F2 mice from a (DU6i x DBA/2)F1 x (DU6i x DBA/2)F1 cross were informative in mapping for loci that had major effects on serum levels of insulin like growth factor binding proteins(IGFBPs). Two QTL markers having major effects were found on mouse Chromosomes 5 and 10. The chromosome 10 QTL designated Igfbp3q2 had an F value of 33.8 and could be placed within a range of between 37 and 51 cMs. The chromosome 5 QTL designated Igfbp3q1 had an F value of 9.92 and could be placed within a range of between 48 and 68 cMs. The authors identified various other suggestive QTLs.

References

• Original: J:68837 Brockmann GA, et al., Genome-wide search for loci controlling serum IGF binding protein levels of mice. FASEB J. 2001 Apr;15(6):978-87
• All: 1 reference(s)