A novel role for transcription factor Lmo4 in thymus development through genetic interaction with Cited2

Dev Dyn. 2010 Jul;239(7):1988-94. doi: 10.1002/dvdy.22334.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Embryo, Mammalian / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • LIM Domain Proteins
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymus Gland / embryology*
  • Thymus Gland / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cited2 protein, mouse
  • Homeodomain Proteins
  • LIM Domain Proteins
  • Lmo4 protein, mouse
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors