Ccdc122__exome

Ccdc122 is a gene of unknown function that was originally linked to inflammatory bowel disease and leprosy. Mouse mutants that are homozygous for a mutant Ccdc122 allele do not show any phenotype in the primary pipeline of the Sanger Mouse Genetics Project. However, data from primary and secondary cohorts suggested a highly significant batch effect for metabolism related phenotypes. In homozygous mice which display a phenotype, energy expenditure was increased by more than 25%, and food intake was increased 35%. In addition, the mice were abnormally lean for their body weights. The phenotype of the hypermetabolic Ccdc122 mice is especially profound due to the degree of the abnormality. The pedigree of all of the mice phenotyped by the MGP can be traced back to a single branch breeding starting with the mouse MEWY7.1c. The colony is also subject to significant amounts of inbreeding. We hypothesize that a secondary de novo mutation arose in the Ccdc122 colony that affected the “hypermetabolic” Ccdc122 mice. This mutation was either subsequently lost, modified or hidden in the colony, meaning that the mice used in subsequent investigations failed to reproduce the hypermetabolic phenotype. The use of exome sequencing on a subset of affected and non-affected mice should allow us to distinguish whether a secondary mutation has occurred and highlight potential mechanisms for the hypermetabolism observed.