Mapping quantitative trait loci that influence serum insulin-like growth factor binding protein-5 levels in F2 mice (MRL/MpJ X SJL/J).

Abstract:

:Recent studies using twins and inbred strains of mice reveal evidence for genetic mechanisms contributing to variation in circulating levels of IGF-I, IGF-II, and IGF binding protein (IGFBP)-3. To examine the hypothesis that serum IGFBP-5 levels have a strong heritable component, we intercrossed two inbred strains of mice, MRL/MpJ and SJL, which exhibit 79% difference in serum IGFBP-5 levels (554 +/- 68 vs. 309 +/- 51 ng/ml respectively, P < 0.001). A genome-wide scan was carried out using 137 polymorphic markers in 633 F2 female mice. Serum IGFBP-5 levels in the F2 progeny showed a normal distribution with an estimated heritability of 74%. Whole genome-wide scans for cosegregation of genetic marker data with high or low serum IGFBP-5 levels revealed six different quantitative trait loci (QTL) in chromosomes 1, 9 (two), 10, and 11 (two), which together explained 24% of F2 variance. Chromosome 11 QTL exhibited the highest LOD score (7.5). Based on the past findings that IGFBP-5 is an important bone formation stimulator, we predicted IGFBP-5 to contribute to bone mineral density variation in F2 mice. Accordingly, we found two of the six IGFBP-5 QTLs (Chrs 1 and 11) identified for serum IGFBP-5 phenotype also showed significant association with total body bone mineral density phenotype (measured by dual energy x-ray absorptiometry) in the F2 mice.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Mohan S,Masinde G,Li X,Baylink DJ

doi

10.1210/en.2003-0042

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

3491-6

issue

8

eissn

0013-7227

issn

1945-7170

journal_volume

144

pub_type

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