A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2.
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.
Michell
Anna C
AC
Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
Bragança
José
J
Broadbent
Carol
C
Joyce
Bradley
B
Franklyn
Angela
A
Schneider
Jürgen E
JE
Bhattacharya
Shoumo
S
Bamforth
Simon D
SD
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*
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