title: Candidate genes required for embryonic development: a comparative analysis of distal mouse chromosome 14 and human chromosome 13q22.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Laurie Jo
authors.initials: LJ
authors.lastname: Kurihara
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Semenova
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ingram
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Guan
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Tilghman
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D017124:Conserved Sequence; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D005796:Genes; D006801:Humans; D051379:Mice; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics* / Q000502:physiology
chemical_list: D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin