Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis.
GATA-3 is one member of a growing family of related transcription factors which share a strongly conserved expression pattern in all vertebrate organisms. In order to elucidate GATA-3 function using a direct genetic approach, we have disrupted the murine gene by homologous recombination in embryonic stem cells. Mice heterozygous for the GATA3 mutation are fertile and appear in all respects to be normal, whereas homozygous mutant embryos die between days 11 and 12 postcoitum (p.c.) and display massive internal bleeding, marked growth retardation, severe deformities of the brain and spinal cord, and gross aberrations in fetal liver haematopoiesis.
Pandolfi
P P
PP
Dept. of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Roth
M E
ME
Karis
A
A
Leonard
M W
MW
Dzierzak
E
E
Grosveld
F G
FG
Engel
J D
JD
Lindenbaum
M H
MH
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D003394:Craniofacial Dysostosis / Q000196:embryology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000002:abnormalities; D005313:Fetal Death / Q000209:etiology; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D005838:Genotype; D005865:Gestational Age; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D008098:Litter Size; D008099:Liver / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000196:embryology; D009421:Nervous System Malformations; D009436:Neural Tube Defects / Q000196:embryology / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors