Faculty Collaboration Database

Identification of genetic determinants of IGF-1 levels and longevity among mouse inbred strains. Aging Cell 2010 Oct;9(5):823-36

Date

08/26/2010

Pubmed ID

20735370

Pubmed Central ID

PMC3025299

DOI

10.1111/j.1474-9726.2010.00612.x

Scopus ID

2-s2.0-78349250620 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

The IGF-1 signaling pathway plays an important role in regulating longevity. To identify the genetic loci and genes that regulate plasma IGF-1 levels, we intercrossed MRL/MpJ and SM/J, inbred mouse strains that differ in IGF-1 levels. Quantitative trait loci (QTL) analysis of IGF-1 levels of these F2 mice detected four QTL on chromosomes (Chrs) 9 (48 Mb), 10 (86 Mb), 15 (18 Mb), and 17 (85 Mb). Haplotype association mapping of IGF-1 levels in 28 domesticated inbred strains identified three suggestive loci in females on Chrs 2 (13 Mb), 10 (88 Mb), and 17 (28 Mb) and in four males on Chrs 1 (159 Mb), 3 (52 and 58 Mb), and 16 (74 Mb). Except for the QTL on Chr 9 and 16, all loci co-localized with IGF-1 QTL previously identified in other mouse crosses. The most significant locus was the QTL on Chr 10, which contains the Igf1 gene and which had a LOD score of 31.8. Haplotype analysis among 28 domesticated inbred strains revealed a major QTL on Chr 10 overlapping with the QTL identified in the F2 mice. This locus showed three major haplotypes; strains with haplotype 1 had significantly lower plasma IGF-1 and extended longevity (P < 0.05) than strains with haplotype 2 or 3. Bioinformatic analysis, combined with sequencing and expression studies, showed that Igf1 is the most likely QTL gene, but that other genes may also play a role in this strong QTL.

Author List

Leduc MS, Hageman RS, Meng Q, Verdugo RA, Tsaih SW, Churchill GA, Paigen B, Yuan R

Author

Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
DNA
Female
Genotype
Insulin-Like Growth Factor I
Longevity
Male
Mice
Mice, Congenic
Mice, Inbred MRL lpr
Oligonucleotide Array Sequence Analysis