Mnek1b^CAST/Ei
QTL Variant Detail

Summary

• QTL variant: Mnek1b^CAST/Ei
• Name: modifier of Nek1 (NIMA-related expressed kinase 1, hematocrit; CAST/Ei
• MGI ID: MGI:2154982
• QTL: Mnek1b Location: unknown Genetic Position: Chr2, Syntenic

Variant origin

• Strain of Specimen: CAST/Ei

Variant description

• Allele Type: QTL
• Inheritance: Recessive

Expression

In Structures Affected by this Mutation:

1 anatomical structure(s)

Notes

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

J:55632

Modifiers of polycystic kidney disease caused by the Nek1^kat-2J mutation were identified using an F2 intercross between CAST/EiJ and C57BL/6J-Nek1^kat-2J. Linkage analysis was performed on F2 intercross animals homozygous for the Nek1^kat-2J mutation. Three significant modifier loci mapped to mouse Chromosomes 1, 2, and 19. Kidney weight and hematocrit were used as quantitative traits for polycystic kidney disease.

Mnek1a mapped to 52 cM on mouse Chromosome 1 near D1Mit8. This locus explains 21.7% of the kidney weight variance and 24.6% of the hematocrit variance. Homozygosity for CAST/EiJ-derived alleles at Mnek1a confers increased kidney weight and decreased hematocrit. Mnek1a interacts with a locus near D10Mit40 (29 cM). Homozygosity for CAST/EiJ at both of these loci significantly increases kidney weight. Mnek1a also interacts with a locus near D4Mit11 (57.4 cM). Homozygosity for CAST/EiJ-derived alleles at Menk1a and C57BL/6J-derived alleles at D4Mit11 significantly decreases hematocrit. Jckm2(55 cM) is a previously identified polycystic kidney disease modifier mapping near Mnek1a. Bcl2 (59.8 cM) is a possible candidate gene for Mnek1a. Homozygous Bcl2 knockout animals exhibit growth retardation and progressive polycystic kidney disease.

Mnek1b mapped to 95.5 cM on mouse Chromosome 2 near D2Mit51. This locus, in conjunction with Mnek1a, explains 34.8% of the hematocrit variance. C57BL/6J-derived alleles at Mnek1b confer decreased hematocrit. The effect of this locus appears to be dominant.

Mnek1c mapped to 41 cM on mouse Chromosome 19 near D19Mit11. This locus, in conjunction with Mnek1a, explains 30.4% of the kidney weight variance. CAST/EiJ-derived alleles at Mnek1c confer increased kidney weight. The effect of this locus appears to be additive. Mnek1c interacts with a locus near D14Mit200 (54.5 cM). Homozygosity for CAST/EiJ-derived alleles at Mnek1c and C57BL/6J-derived alleles at D14Mit200 significantly increases kidney weight.

References

• Original: J:55632 Upadhya P, et al., Genetic modifiers of polycystic kidney disease in intersubspecific KAT2J mutants. Genomics. 1999 Jun 1;58(2):129-37
• All: 1 reference(s)