RGD Reference Report - QTLs influencing IGF-1 levels in a LOU/CxFischer 344F2 rat population. Tracks towards the metabolic theory of Ageing. - Rat Genome Database

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QTLs influencing IGF-1 levels in a LOU/CxFischer 344F2 rat population. Tracks towards the metabolic theory of Ageing.

Authors: Marissal-Arvy, N  Duron, E  Parmentier, F  Zizzari, P  Mormede, P  Epelbaum, J 
Citation: Marissal-Arvy N, etal., Growth Horm IGF Res. 2013 Dec;23(6):220-8. doi: 10.1016/j.ghir.2013.08.002. Epub 2013 Aug 19.
RGD ID: 7794844
Pubmed: (View Article at PubMed) PMID:24028904
DOI: Full-text: DOI:10.1016/j.ghir.2013.08.002

OBJECTIVE: Since a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (and diet)-induced obesity. DESIGN: F1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were bred inter se to obtain the F2 population, of which 93 males and 94 females were studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome scan of the F2 population was made with 100 microsatellite markers) selected for their polymorphism between LOU/C and F344 strains (and by covering evenly the whole genome. RESULTS: By simple interval mapping sex-dependent QTLs were found on chromosome 17 in males and on chromosome 18 in females. By multiple interval mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and D12Mgh5 were found in both males and females. The majority of QTLs corresponded to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A significant proportion of these genes are connected to IGF-1 production and receptor pathways (n = 18) or metabolic syndrome (n = 11). CONCLUSIONS: Subsequent studies are necessary to determine whether the genetic networks underscored are also involved in age-associated obesity, diabetes and inflammation as well as cardiovascular impairments.

Annotation

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Mammalian Phenotype
Phenotype Values via PhenoMiner

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Objects Annotated

QTLs
Pigfal1  (Plasma insulin-like growth factor 1 level QTL 1)
Pigfal10  (Plasma insulin-like growth factor 1 level QTL 10)
Pigfal11  (Plasma insulin-like growth factor 1 level QTL 11)
Pigfal12  (Plasma insulin-like growth factor 1 level QTL 12)
Pigfal13  (Plasma insulin-like growth factor 1 level QTL 13)
Pigfal14  (Plasma insulin-like growth factor 1 level QTL 14)
Pigfal15  (Plasma insulin-like growth factor 1 level QTL 15)
Pigfal16  (Plasma insulin-like growth factor 1 level QTL 16)
Pigfal17  (Plasma insulin-like growth factor 1 level QTL 17)
Pigfal18  (Plasma insulin-like growth factor 1 level QTL 18)
Pigfal19  (Plasma insulin-like growth factor 1 level QTL 19)
Pigfal2  (Plasma insulin-like growth factor 1 level QTL 2)
Pigfal3  (Plasma insulin-like growth factor 1 level QTL 3)
Pigfal4  (Plasma insulin-like growth factor 1 level QTL 4)
Pigfal5  (Plasma insulin-like growth factor 1 level QTL 5)
Pigfal6  (Plasma insulin-like growth factor 1 level QTL 6)
Pigfal7  (Plasma insulin-like growth factor 1 level QTL 7)
Pigfal8  (Plasma insulin-like growth factor 1 level QTL 8)
Pigfal9  (Plasma insulin-like growth factor 1 level QTL 9)


Additional Information