Phenotype-Based Search of Natural Mutations Related to Hereditary Diseases Existing in a Closed Colony of Mice

Abstract

Abstract:We attempted to detect natural mutations existing in the Jcl:ICR closed colony of mice which is maintained by random mating. We used ordinary genetic backcrosses to efficiently detect recessive mutations carried by individual mice in the colony. Crosses of DBA/2 females and ICR males were performed to obtain F 1 mice. Four F 1 females randomly selected from each cross were backcrossed to the male parent. More than thirty backcross progeny were obtained from each F 1 female by several deliveries. Phenotypes of the backcross progeny were observed macroscopically at about one month of age. As a result, 18 (26.1%) of 69 Jcl:ICR males carried 11 recessive mutation(s). Based on the phenotypes, the tentative names were abnormal kidney, aplasia of eyelids/hind limb digits, circling, dwarfism, heterotaxy, hind limb paralysis, hydrocephalus, rigidity (or rigor), testicular hypoplasia, tremor, and wobbling. The genes responsible for aplasia of eyelids/hind limb digits and dwarfism were each carried by two males, the genes responsible for hydrocephalus and testicular hypoplasia were each carried by three males and the gene responsible for wobbling by four males. It was strongly suggested that the genes shared by several males originated from an identical mutated gene. Surprisingly, male No. 43 had the responsible genes of abnormal kidneys and testicular hypoplasia, and No. 79 had those of dwarfism and tremor. The results obtained in this study suggest that breeders need to be aware of the presence of natural mutations in their colonies.

A New <i>Enpp1</i> allele, <i>Enpp1</i><i>^ttw-Ham</i>, Identified in an ICR Closed Colony

“…The gene responsible was mapped to chromosome 10 [21]. In this study, we performed sequencing in order to demonstrate that this genetic mutation caused ankylosis.…”

“…A novel mutation causing ankylosis was carried by the Jcl:ICR #48 male mouse [21]. A congenic strain carrying Enpp1 ttw-Ham was generated by backcrossing to transfer the ankylotic responsible gene into the C57BL/6JJcl strain.…”

“…Recently, we discovered an autosomal recessive gene causing ankylosis in a Jcl:ICR male mouse closely linked to the Enpp1 gene on chromosome 10 [21]. Mice homozygous for this gene are characterized by tiptoe walking, stiffness of the vertebral column and limb joints, and progressive hypercalcification.…”

A Novel <i>Kit</i> Gene Mutation in CF1 Mice Involved in the Extracellular Domain of the KIT Protein

“…Recently, we developed a system to find natural mutations in Jcl:iCR closed colony mice that are maintained by random mating [12]. in this study, we applied a natural mutation screening system to the Crl:CF1 closed colony.…”