Tcnq3^NOD
QTL Variant Detail

Summary

• QTL variant: Tcnq3^NOD
• Name: Tgfb1 trangenic F2 between C3H and NOD QTL 3; NOD
• MGI ID: MGI:3831715
• QTL: Tcnq3 Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: NOD

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Notes

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

J:130968

Genetic modifiers of diabetes phenotypes exacerbated by the presence of a Tgfb1 transgene were mapped using F2 crosses involving NOD, C3H/HeJJcl and DBA/2JJcl. NOD-Tg(Gcg-TGFB1)1Itak animals were bred to either C3H/HeJJcl or DBA/2JJcl and then intercrossed to create 198 (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 animals and 241 (NOD-Tg(Gcg-TGFB1)1Itak x DBA/2JJcl)F2 animals. All F2 animals were homozygous for the transgene and phenotyped at 8 weeks of age for body weight, blood glucose concentration, glucose tolerance and serum insulin concentration. Males from parental strain NOD-Tg(Gcg-TGFB1)1Itak display decreased body weight and increased blood glucose concentrations at 0 and 30 minutes during the glucose tolerance test compared to male non-transgenic NOD animals, DBA/2JJcl and C3H/HeJJcl. Female NOD-Tg(Gcg-TGFB1)1Itak animals have increased blood glucose concentration at 30 minutes in the glucose tolerance test compared to female C3H/HeJJcl and DBA/2JJcl animals. A panel of 313 polymorphic markers was usedto screen the NOD x C3H/HeJJcl population and 289 markers were used to screen the NOD x DBA/2JJcl population.

A female-specific locus for serum insulin concentration at 30 minutes into the glucose tolerance test mapped to 22.3 cM on mouse Chromosome1 near D1Mit18 (LOD=4.41) in the (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 population. This locus is named Tcnq1 (Tgfb1 transgenic F2 between C3H and NOD QTL 1). C3H/HeJJcl-derived alleles at Tcnq1 confer increased serum insulin in females with an additivemode of inheritance. Insq6 (37 cM) and Idd26 (20 cM) are previously identified diabetes QTLs located near Tcnq1. Mstn (27.8 cM) and Hspe1 are potential candidate genes for Tcnq1.

Tcnq2 (Tgfb1 transgenic F2 between C3H and NOD QTL 2) mapped to 54 cM on mouse Chromosome 7 near D7Mit321 (LOD=4.38) in the (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 population. This female-specific locus is associated with blood glucose concentration at 30 minutes into the glucose tolerance test. C3H/HeJJcl-derived alleles at Tcnq2 confer dominantly inherited increase in blood glucose concentration in females. Nidd1k (49 cM) and Idd27 (47 cM) are previously identified QTLs located near Tcnq2. Potential candidate genes include Ucp2 (50 cM), Ucp3 (50 cM) and Calca (54 cM). Ucp2 mRNAexpression in soleus muscle appears to be linked to the Tcnq2 locus (LOD=4.9). NOD-derived alleles affect Ucp2 mRNA expression in a dominant manner.

Significant linkage to body weight at 8 weeks in males mapped to 75.6 cM on mouseChromosome 2 near D2Mit287 (LOD=4.94). This locus was identified in the (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 population and is named Tcnq3 (Tgfb1 transgenic F2 between C3H and NOD QTL 3). C3H/HeJJcl-derived alleles at Tcnq3 confer increased male bodyweight in a dominant manner. Idd13 (71 cM) is a previously identified diabetes QTL located near Tcnq3. Hnf4a (94 cM) and Ghrh (89 cM) are possible candidate genes for Tcnq3.

Tcnq4 (Tgfb1 transgenic F2 between C3H and NOD QTL 4) was identified in the (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 population and maps to 33.8 cM on mouse Chromosome 14 near D14Mit123 and D14Mit5. This locus is associated with blood glucose concentrations in males at 0 minutes (LOD=3.99) and 120 minutes (LOD=3.78) into the glucosetolerance test. NOD-derivedalleles at Tcnq4 confer increased blood glucose concentrations in males with a recessive mode of inheritance. Nidd2n (22.5 cM) is a previously identified diabetes QTL that overlaps with the Tcnq4 locus. Pck2 (21 cM) and Gnrh1 (30.5 cM) are potential candidate genes for Tcnq4.

Tcnq5 (Tgfb1 transgenic F2 between C3H and NOD QTL 5) mapped to 43.6 cM on mouse Chromosome 18 near D18Mit7 in the (NOD-Tg(Gcg-TGFB1)1Itak x C3H/HeJJcl)F2 population. This locus is associated with serum insulin concentration in males at 30 minutes into the glucose tolerance test (LOD=4.99). C3H/HeJJcl-derived alleles at Tcnq5 confer increased serum insulin in males with a recessive mode of inheritance. Mbp (55 cM) and Mc4r are potential candidate genes forTcnq5.

Significant linkage to body weight at 8 weeks in males mapped to 27.5 cM on mouse Chromosome 13 near D13Mit54 (LOD=4.39) in the (NOD-Tg(Gcg-TGFB1)1Itak x DBA/2JJcl)F2 population and is named Tdnq1 (Tgfb1 transgenic F2 between DBA and NOD QTL 1).DBA/2JJcl-derived alleles atTdnq1 confer dominant increase in body weight in males. Idd14 (22 cM) is a previously identified diabetes QTL located near Tdnq1. Potential candidate genes for Tdnq1 include Prl (14 cM) and Dok3.

References

• Original: J:130968 Suzuki T, et al., Diabetic modifier QTLs in F(2) intercrosses carrying homozygous transgene of TGF-beta. Mamm Genome. 2008 Jan;19(1):15-25
• All: 1 reference(s)