Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-5-20
pubmed:abstractText
Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c. ) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1417-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10068635-Animals, pubmed-meshheading:10068635-Brain, pubmed-meshheading:10068635-Cell Division, pubmed-meshheading:10068635-Ear, pubmed-meshheading:10068635-Electroencephalography, pubmed-meshheading:10068635-Epilepsy, pubmed-meshheading:10068635-Gene Expression Regulation, Developmental, pubmed-meshheading:10068635-Histocytochemistry, pubmed-meshheading:10068635-Homeodomain Proteins, pubmed-meshheading:10068635-Humans, pubmed-meshheading:10068635-In Situ Hybridization, pubmed-meshheading:10068635-Mice, pubmed-meshheading:10068635-Mice, Knockout, pubmed-meshheading:10068635-Nerve Tissue Proteins, pubmed-meshheading:10068635-Otx Transcription Factors, pubmed-meshheading:10068635-Phenotype, pubmed-meshheading:10068635-RNA, Messenger, pubmed-meshheading:10068635-Semicircular Canals, pubmed-meshheading:10068635-Trans-Activators, pubmed-meshheading:10068635-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes.
pubmed:affiliation
International Institute of Genetics and Biophysics, CNR, Via G. Marconi 12, Italy. simeone@iigbna.iigb.na.cnr.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't