Ckdbp2^{129S6/SvEvTac}
QTL Variant Detail

Summary

• QTL variant: Ckdbp2^{129S6/SvEvTac}
• Name: chronic kidney disease blood pressure locus 2; 129S6/SvEvTac
• MGI ID: MGI:3766472
• QTL: Ckdbp2 Location: Chr11:54080941-65103841 bp Genetic Position: Chr11, cM position of peak correlated region/allele: 32.13 cM
• QTL Note: genome coordinates based on the boundaries of the QTL region

Variant origin

• Strain of Specimen: 129S6/SvEvTac

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased blood pressure and albuminuria compared to C57BL/6J. (J:127712)
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

2 anatomical structure(s)

Notes

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

J:127712

Linkage analysis was performed on 44 (129S6/SvEvTac x C57BL/6J)F2 animals to identify QTLs associated with chronic kidney disease. Experimental animals were partially nephrectomized at age 4- to 6-weeks and phenotyped between 7- to 10-weeks. A panel of 96 microsatellite markers spaced 15 cM - 20 cM apart was used for the genome scan. Parental strain 129S6/SvEvTac displays significant susceptibility to hypertension, albuminuria, and kidney injury whereas C57BL/6J is resistant.

Linkage to blood pressure mapped to 62.1 cM on mouse Chromosome 1 (LOD=3.8 near D1Mit308) and is named Ckdbp1 (chronic kidney disease blood pressure locus 1). 129S6/SvEvTac-derived alleles at Ckdbp1 confer increased blood pressure and the mode of inheritance is appears to be recessive. The Ckdbp1 QTL interval spans 43 cM to 73 cM. This locus explains 21% of the blood pressure variance.

Ckdbp2 (chronic kidney disease blood pressure locus 2) mapped to 32 cM on mouse Chromosome 11 near D11Mit143 (LOD=4.8). This locus explains 39% of the blood pressure variance and was replicated in a separate set of 27 F2 animals. The Cdkbp2 QTL interval is an 8 cM region flanked by D11Mit86 (28 cM) and D11Mit177 (36 cM). 129S6/SvEvTac-derived alleles at Ckdbp2 confer increased blood pressure with recessive inheritance. Albuminuria susceptibility overlaps with the Ckdbp2 locus (LRS=11.4). 129S6/SvEvTac-derived alleles at Ckdbp2 are correlated with increased urinary albumin/creatine ratio with a recessive effect. A previously identified blood pressure QTL named Abbp4 (54 cM) maps near Ckdbp2. The Ckdbp2 locus is syntenic to regions on rat Chromosome 10 and human Chromosome 17 that have been linked to hypertension. Wnk4 is a potential candidate gene for Ckdbp2. Mutations in this gene have been reportedin human hypertension.

Suggestive linkage to glomerulonephritis mapped to 86 cM on mouse Chromosome 2 with LRS=13.7 at D2Mit285.

References

• Original: J:127712 Salzler HR, et al., Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus. Kidney Int. 2007 Nov;72(10):1226-32
• All: 1 reference(s)