Generation and standardized, systemic phenotypic analysis of Kctd1 mutant mice

Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically mutant line HST014 was established and further analyzed. The causative mutation was detected in the gene Kctd1 which leads to the amino acid exchange Kctd1I27N thereby affecting the functional BTB domain of the protein. This line is the first mouse model harbouring a Kctd1 mutation. Kctd1I27N homozygous mutant mice die perinatally. Standardized, systemic phenotypic analysis of heterozygous mutants was carried out in the German Mouse Clinic. Systematic morphological investigation of the external physical appearance found no mutation-specific differences. Main phenotypic changes were kidney dysfunction, minor cardiovascular and neurological alterations as well as low plasma corticosterone levels. Genome-wide RNA expression analysis at the age of 4 months revealed few regulated genes in brain and heart, and over 100 significantly regulated genes in kidneys of heterozygous mutants.

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