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A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2
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Dr Simon Bamforth
Michell A, Braganca J, Broadbent C, Joyce B, Franklyn A, Schneider JE, Bhattacharya S, Bamforth SD
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Deletion of the transcriptional modulator Cited2 in the mouse results in embryonic lethality, cardiovascularmalformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left–right patterningdefects, all seen with a varying degree of penetrance. The phenotypic heterogeneity, observed on differentgenetic backgrounds, indicates the existence of both genetic and environmental modifiers. Mice lackingthe LIM domain-containing protein Lmo4 share specific phenotypes with Cited2 null embryos, such as embryoniclethality, cranial ganglia fusion, and exencephaly. These shared phenotypes suggested that Lmo4may be a potential genetic modifier of the Cited2 phenotype. Examination of Lmo4-deficient embryosrevealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination ofLmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 incontrol of thymus development. Our data suggest that this may occur, in part, through control of expressionof a common target gene, Tbx1, which is necessary for normal thymus development.
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