Isolation and characterization of two mouse mutants with developmental defects

• Main Author: Mitchell, Karen
• Published: University of Manchester 2009
• Subjects: 576.549
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502262

Congenital abnormalities can be modeled in the mouse using genetic approaches such as phenotype driven mutagenesis screens. Mouse N-Ethyl-N-nitrousea (ENU) mutagenesis screens create point mutations throughout the genome and can be employed to elucidate the function of genes that are conserved between the mouse and human. Region-specific mutagenesis screens can determine the functional content of a defined chromosomal region based on the mutant phenotypes isolated. A region-specific mutagenesis screen directed at mouse chromosome 11 allowed the isolation of the 111Jus27 mutant. Two separate embryonic lethal mutations have been isolated from the lllJus27 mouse line named K27 and embryonic hydrocephalus (EHC). The K27 mouse mutant has defective cardiovascular development causing lethality at mid-gestation. Morphological analysis revealed that pericardial effusion and abnormal cardiac looping are prevalent in K27 mutants. Furthermore, expression analysis indicates that the K27 mutation also causes a disruption in cardiac myogenesis. Meiotic mapping has refined the K27 candidate interval to 5Mb.