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PMID:14966286

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Citation

Hahm, K, Sum, EY, Fujiwara, Y, Lindeman, GJ, Visvader, JE and Orkin, SH (2004) Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1. Mol. Cell. Biol. 24:2074-82

Abstract

LMO4 belongs to a family of transcriptional regulators that comprises two zinc-binding LIM domains. LIM-only (LMO) proteins appear to function as docking sites for other factors, leading to the assembly of multiprotein complexes. The transcription factor Deaf-1/NUDR has been identified as one partner protein of LMO4. We have disrupted the Lmo4 and Deaf-1 genes in mice to define their biological function in vivo. All Lmo4 mutants died shortly after birth and showed defects within the presphenoid bone, with 50% of mice also exhibiting exencephaly. Homeotic transformations were observed in Lmo4-null embryos and newborn mice, but with incomplete penetrance. These included skeletal defects in cervical vertebrae and the rib cage. Furthermore, fusions of cranial nerves IX and X and defects in cranial nerve V were apparent in some Lmo4(-/-) and Lmo4(+/-) mice. Remarkably, Deaf-1 mutants displayed phenotypic abnormalities similar to those observed in Lmo4 mutants. These included exencephaly, transformation of cervical segments, and rib cage abnormalities. In contrast to Lmo4 nullizygous mice, nonexencephalic Deaf-1 mutants remained healthy. No defects in the sphenoid bone or cranial nerves were apparent. Thus, Lmo4 and Deaf-1 mutant mice exhibit overlapping as well as distinct phenotypes. Our data indicate an important role for these two transcriptional regulators in pathways affecting neural tube closure and skeletal patterning, most likely reflecting their presence in a functional complex in vivo.

Links

PubMed PMC350571

Keywords

Adaptor Proteins, Signal Transducing; Animals; Animals, Newborn; Body Patterning; Bone and Bones/abnormalities; Central Nervous System/abnormalities; Central Nervous System/embryology; Central Nervous System/physiology; Cranial Nerves/abnormalities; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryo, Mammalian/anatomy & histology; Embryo, Mammalian/pathology; Embryo, Mammalian/physiology; Gene Targeting; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; LIM Domain Proteins; Mice; Mice, Knockout; Morphogenesis/physiology; Sphenoid Bone/abnormalities; Sphenoid Bone/embryology; Transcription Factors/genetics; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DEAF1

involved_in

GO:0001843: neural tube closure

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DEAF1

involved_in

GO:0048706: embryonic skeletal system development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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Internal error - GONUTS

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[9eb37796537cd8c4fe1bbb37] /wiki/index.php/PMID:14966286 Error from line 252 of /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php: Call to a member function getIdentifier() on null

Backtrace:

#0 /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php(70): AnnotationLinks::getQuickGOannotations(string, array)
#1 /var/www/html/go/wiki/includes/parser/Parser.php(3888): AnnotationLinks::renderAnnotations(NULL, array, Parser, PPFrame_DOM)
#2 /var/www/html/go/wiki/includes/parser/Preprocessor_DOM.php(1362): Parser->extensionSubstitution(array, PPFrame_DOM)
#3 /var/www/html/go/wiki/includes/parser/Parser.php(2942): PPFrame_DOM->expand(DOMElement, integer)
#4 /var/www/html/go/wiki/includes/parser/Parser.php(1293): Parser->replaceVariables(string)
#5 /var/www/html/go/wiki/includes/parser/Parser.php(443): Parser->internalParse(string)
#6 /var/www/html/go/wiki/includes/content/WikitextContent.php(323): Parser->parse(string, Title, ParserOptions, boolean, boolean, integer)
#7 /var/www/html/go/wiki/includes/content/AbstractContent.php(516): WikitextContent->fillParserOutput(Title, integer, ParserOptions, boolean, ParserOutput)
#8 /var/www/html/go/wiki/includes/content/ContentHandler.php(1324): AbstractContent->getParserOutput(Title, integer, ParserOptions)
#9 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(348): ContentHandler->getParserOutputForIndexing(WikiPage, ParserCache)
#10 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(407): CirrusSearch\Updater::buildDocument(CirrusSearch, WikiPage, CirrusSearch\Connection, integer, integer, integer)
#11 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(205): CirrusSearch\Updater->buildDocumentsForPages(array, integer)
#12 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Updater.php(83): CirrusSearch\Updater->updatePages(array, integer)
#13 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Job/LinksUpdate.php(52): CirrusSearch\Updater->updateFromTitle(Title)
#14 /usr/local/github/wiki-extensions/wiki-extensions-hulab/CirrusSearch/includes/Job/Job.php(99): CirrusSearch\Job\LinksUpdate->doJob()
#15 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(296): CirrusSearch\Job\Job->run()
#16 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(193): JobRunner->executeJob(CirrusSearch\Job\LinksUpdate, Wikimedia\Rdbms\LBFactorySimple, BufferingStatsdDataFactory, integer)
#17 /var/www/html/go/wiki/includes/MediaWiki.php(1002): JobRunner->run(array)
#18 /var/www/html/go/wiki/includes/MediaWiki.php(988): MediaWiki->triggerSyncJobs(integer, MediaWiki\Logger\LegacyLogger)
#19 /var/www/html/go/wiki/includes/MediaWiki.php(912): MediaWiki->triggerJobs()
#20 /var/www/html/go/wiki/includes/MediaWiki.php(727): MediaWiki->restInPeace(string, boolean)
#21 /var/www/html/go/wiki/includes/MediaWiki.php(750): MediaWiki->{closure}()
#22 /var/www/html/go/wiki/includes/MediaWiki.php(557): MediaWiki->doPostOutputShutdown(string)
#23 /var/www/html/go/wiki/index.php(42): MediaWiki->run()
#24 {main}

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