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Nafldq1BTBR/J
QTL Variant Detail
Nomenclature
QTL variant: Nafldq1BTBR/J
Name: nonalcoholic fatty liver disease QTL 1; BTBR/J
MGI ID: MGI:5792707
Synonyms: Nafldq1BTBR T+ Itpr3tf/J
QTL: Nafldq1  Location: unknown  Genetic Position: Chr17, Syntenic
Variant
origin
Strain of Specimen:  BTBR T+ Itpr3tf/J
Variant
description
Allele Type:    QTL
Inheritance:    Not Specified
Notes

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

J:186560

The C57BL/6J strain, when made obese, is relatively resistant to diabetes, whereas the BTBR T+ Itpr3tf/J strain develops severe diabetes when made obese due to a failure to expand beta-cell mass and to a defect in insulin secretion. Linkage analysis was performed on a mapping population of 550 (B6.Cg-Lepob x BTBR.Cg-Lepob)F2-Lepob/Lepob mice to identify QTL related to nonalchoholic fatty liver disease. Mice were genotyped with the 5K GeneChip (Affymetrix). One QTL reaching genome-wide significance was identified:

QTL Nafldq1 (nonalcoholic fatty liver disease QTL 1) maps to Chromosome 17 with a peak LOD score of 15.0 at 42.0 Mb (0 - 16 Mb confidence interval). F2 mice homozygous for the C57BL/6J allele at the Nafldq1 locus had an approximately 2-fold higher liver triglyceride content than mice with homozygous BTBR T+ Itpr3tf/J genotype (P 0.0001). Heterozygotes displayed an intermediate phenotype.

Tsc2 is the reported candidate gene underlying Nafldq1. Tsc2 functions as an inhibitor of mammalian target of rapamycin, which is involved in many physiological processes, including cell growth, proliferation, and metabolism. The authors sequenced the C57BL/6J and BTBR T<+ Itpr3tf/J alleles of the Tsc2 gene and found a nonsynonymous coding SNP (M552V), located at an unexplored region of the protein. They show that this coding difference causes the C57BL/6J form of Tsc2 to inhibit mTORC1 less efficiently than the BTBR T+ Itpr3tf/J form and therefore causes increased de novo lipogenesis in the liver.

References
Original:  J:186560 Wang CY, et al., Tsc2, a positional candidate gene underlying a quantitative trait locus for hepatic steatosis. J Lipid Res. 2012 Aug;53(8):1493-1501
All:  1 reference(s)

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last database update
06/28/2022
MGI 6.20
The Jackson Laboratory