Mpdk6^CAST/Ei
QTL Variant Detail

Summary

• QTL variant: Mpdk6^CAST/Ei
• Name: modifier of polycystic kidney disease 6; CAST/Ei
• MGI ID: MGI:3603243
• QTL: Mpdk6 Location: unknown Genetic Position: Chr13, Syntenic

Variant origin

• Strain of Specimen: CAST/Ei

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased biliary ductal expansion compared to C57BL/6J. (J:99468)
• Inheritance: Other (see notes)

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

This allele exhibits overdominance.

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

J:99468

Linkage analysis was performed on 461 homozygous mutant animals from a (C57BL/6J-Cys1^cpk x CAST/Ei)F2 intercross to identify modifiers of the Cys1^cpk mutation. 79 microsatellite markers at an average spacing of 25 cM were used in the genome scan. C57BL/6J-Cys1^cpk mutant animals exhibit cystic kidney disease and biliary dysgenesis.

Major modifier loci mapped to 16 cM, 34 cM, and 54 cM on mouse Chromosome 4 in linkage to renal traits and biliary ductal expansion. These loci are named Mpdk1 (modifierof polycystic kidney disease 1), Mpdk2, and Mpdk3, respectively. Mpdk3 also shows linkage to cholangitis (LOD=4.8). CAST/Ei-derived alleles at Mpdk1, Mpdk2, and Mpdk3 confer increased renal traits (kidney length, weight, and volume) with a dominant mode of inheritance. Kif12 maps to the Mpdk2 region and is proposed as a candidate gene. The C57BL/6J allele of Kif12 has a 15 bp deletion corresponding to a 5 amino acid deletion in the predicted L2 loop of the kinesin molecular motor catalytic domain. In addition, the CAST/Ei Kif12 haplotype shows strong correlation with polycystic kidney disease severity in (C57BL/6J-Cys1^cpk x CAST/Ei)F2 mice.

Linkage to renal traits mapped to 26 cM on mouse Chromosome 1 with LOD=2.5. This locus is named Mpdk4 (modifier of polycystic kidney disease 4). CAST/Ei-derived alleles at Mpdk4 confer increased renal traits with an additive mode of inheritance.

Linkage to renal traits mapped to 8 cM on mouse Chromosome 2 with LOD=3.2. This locus is named Mpdk5 (modifier of polycystic kidney disease 5). CAST/Ei-derived alleles at Mpdk5 confer increased renal traits with an additive mode of inheritance.

Linkage to biliary ductal expansion mapped to 16 cM on mouse Chromosome 13 with LOD=6.8. This locus is named Mpdk6 (modifier ofpolycystic kidney disease 6) and exhibits overdominance.

Linkage to cholangitis mapped to 40 cM on mouse Chromosome 19 with LOD=2.7. This locus is named Mpdk7 (modifier of polycystic kidney disease 7). CAST/Ei-derived alleles at Mpdk7 confer increased cholangitis with an additive mode of inheritance.

Linkage to cholangitis mapped to 6 cM on mouse Chromosome 3 with LOD=3.3. This locus is named Mpdk8 (modifier of polycystic kidney disease 8). CAST/Ei-derived alleles at Mpdk8 confer increased cholangitis with an additive mode of inheritance.

Interaction between loci at 62 cM on mouse Chromosome 1 and 96 cM on mouse Chromosome 2 was detected for effects on biliary duct expansion. A second interacting locus pair affecting biliary duct expansionwas detected between 14 cM on mouse Chromosome 4 and 17 cM on mouse Chromosome 18.

References

• Original: J:99468 Mrug M, et al., Kinesin family member 12 is a candidate polycystic kidney disease modifier in the cpk mouse. J Am Soc Nephrol. 2005 Apr;16(4):905-16
• All: 1 reference(s)