TitleCandidate genes required for embryonic development: a comparative analysis of distal mouse chromosome 14 and human chromosome 13q22.
Publication TypeJournal Article
Year of Publication2002
AuthorsKurihara, LJo, Semenova, E, Miller, W, Ingram, RS, Guan, X-J, Tilghman, SM
Date Published2002 Feb
KeywordsAnimals, Chromosome Mapping, Chromosomes, Human, Pair 13, Conserved Sequence, Embryonic and Fetal Development, Exons, Gene Deletion, Genes, Humans, Mice, Receptor, Endothelin B, Receptors, Endothelin

Mice homozygous for the Ednrb(s-1Acrg) deletion arrest at embryonic day 8.5 from defects associated with mesoderm development. To determine the molecular basis of this phenotype, we initiated a positional cloning of the Acrg minimal region. This region was predicted to be gene-poor by several criteria. From comparative analysis with the syntenic human locus at 13q22 and gene prediction program analysis, we found a single cluster of four genes within the 1.4-to 2-Mb contig over the Acrg minimal region that is flanked by a gene desert. We also found 130 highly conserved nonexonic sequences that were distributed over the gene cluster and desert. The four genes encode the TBC (Tre-2, BUB2, CDC16) domain-containing protein KIAA0603, the ubiquitin carboxy-terminal hydrolase L3 (UCHL3), the F-box/PDZ/LIM domain protein LMO7,and a novel gene. On the basis of their expression profile during development, all four genes are candidates for the Ednrb(s-1Acrg) embryonic lethality. Because we determined that a mutant of Uchl3 was viable, three candidate genes remain within the region.

Alternate JournalGenomics