An essential gene mutagenesis screen across the highly conserved piebald deletion region of mouse chromosome 14.
The piebald deletion complex is a set of overlapping chromosomal deficiencies on distal mouse chromosome 14. We surveyed the functional genetic content of the piebald deletion region in an essential gene mutagenesis screen of 952 genomes to recover seven lethal mutants. The ENU-induced mutations were mapped to define genetic intervals using the piebald deletion panel. Lethal mutations included loci required for establishment of the left-right embryonic axis and a loss-of-function allele of Phr1 resulting in respiratory distress at birth. A functional map of the piebald region integrates experimental genetic data from the deletion panel, mutagenesis screen, and the targeted disruption of specific genes. A comparison of several genomic intervals targeted in regional mutagenesis screens suggests that the piebald region is characterized by a low gene density and high essential gene density with a distinct genomic content and organization that supports complex regulatory interactions and promotes evolutionary stability.
Hagarman
James A
JA
Department of Biomedical Sciences, Cornell University, Ithaca, New York.
O'Brien
Timothy P
TP
D000477:Alkylating Agents / Q000633:toxicity; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004252:DNA Mutational Analysis; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D020043:Genes, Essential; D005804:Genes, Lethal; D005838:Genotype; D008171:Lung Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics*; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases
D000477:Alkylating Agents; D002352:Carrier Proteins; C532954:Mycbp2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D005038:Ethylnitrosourea