Rtmq1^Ibut:AIRL
QTL Variant Detail

Summary

• QTL variant: Rtmq1^Ibut:AIRL
• Name: renal tumor modifier QTL 1; Ibut:AIRH
• MGI ID: MGI:5902094
• QTL: Rtmq1 Location: Chr17:22900036-25721472 bp Genetic Position: Chr17, Syntenic

Variant origin

• Strain of Specimen: Ibut:AIRL

Variant description

• Allele Type: QTL

Notes

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

J:237470

The genetic basis of susceptibility to renal tumorigenesis has not yet been established in mouse strains. Mouse lines derived by bidirectional phenotypic selection on the basis of their maximal Ibut:AIRH (AIRmax) or minimal Ibut:AIRL (AIRmin) acute inflammatory responsiveness differ widely in susceptibility to spontaneous and urethane-induced renal tumorigenesis. To map the functional loci modulating renal tumor susceptibility in these mice, a genome-wide genetic linkage study, using SNP arrays, in an (AIRmax x AIRmin)F2 intercross population treated with a single urethane dose at 1 week of age and phenotyped for renal tumors at 35 weeks of age was performed.

AIRmax mice did not develop renal tumors spontaneously nor in response to urethane, whereas in AIRmin mice renal tumors formed spontaneously (in 52% of animals) and after urethane induction (89%). The tumors had a papillary morphology and were positive for alpha-methylacyl-CoA racemase and negative for CD10.

Analysis of 879 informative SNPs in 662 (AIRmax x AIRmin)F2 mice, identified a single quantitative trait locus modulating the incidence of renal tumors in the intercross population.

QTL Rtmq1 (renal tumor modifier QTL 1), mapped to chromosome 17 at 23.4 Mb (LOD score = 15.8), with SNPs rs3696835 and rs3719497 flanking the LOD score peak. The A allele of rs3719497 from AIRmin mice was associated with a 2.5-fold increased odds ratio for renal tumor development.

The LOD score peak included the Tuberous sclerosis 2 (Tsc2) gene which has already been implicated in kidney disease: loss of function by germline retroviral insertion is associated with spontaneous renal tumorigenesis in the Eker rat, and heterozygous-null Tsc2(+/) mice develop renal cystadenomas.

References

• Original: J:237470 Jensen JR, et al., Genetic control of renal tumorigenesis by the mouse Rtm1 locus. BMC Genomics. 2013 Oct 22;14:724
• All: 1 reference(s)