title: A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2.
abstract: Deletion of the transcriptional modulator Cited2 in the mouse results in embryonic lethality, cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects, all seen with a varying degree of penetrance. The phenotypic heterogeneity, observed on different genetic backgrounds, indicates the existence of both genetic and environmental modifiers. Mice lacking the LIM domain-containing protein Lmo4 share specific phenotypes with Cited2 null embryos, such as embryonic lethality, cranial ganglia fusion, and exencephaly. These shared phenotypes suggested that Lmo4 may be a potential genetic modifier of the Cited2 phenotype. Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of expression of a common target gene, Tbx1, which is necessary for normal thymus development.
authors.affiliation: Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Michell
authors.forename: José
authors.initials: J
authors.lastname: Bragança
authors.forename: Carol
authors.initials: C
authors.lastname: Broadbent
authors.forename: Bradley
authors.initials: B
authors.lastname: Joyce
authors.forename: Angela
authors.initials: A
authors.lastname: Franklyn
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Simon D
authors.initials: SD
authors.lastname: Bamforth
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000196:embryology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110087:Cited2 protein, mouse; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors