Disease relevance of Hod

• Transgenic mice that overexpress Hop develop severe cardiac hypertrophy, cardiac fibrosis, and premature death [1].
• Treatment of Hop transgenic mice with trichostatin A, an HDAC inhibitor, prevents hypertrophy [1].
• Much of the parental small-plaque Toto 1101 strain of Sindbis virus was cleared from the circulation by the liver within minutes, in contrast to recombinant large-plaque viruses, which had longer circulating half-lives [2].
• While Toto 50 also replicated in similar tissues, the extent of replication was severely restricted and mice developed lesions characteristic of encephalitis [3].

High impact information on Hod

• Genetic and biochemical data indicate that Hop functions directly downstream of Nkx2-5 [4].
• Inactivation of Hop in mice by homologous recombination results in a partially penetrant embryonic lethal phenotype with severe developmental cardiac defects involving the myocardium [4].
• Thus Hop is regulated in the forebrain by a so far unidentified paracrine signaling factor from the roof plate [5].
• The smallest known homeodomain protein, Homeodomain only protein (Hop), was identified and described here as a temporally and spatially restricted gene in the neurogenic regions of the developing murine CNS including the cerebral cortex [5].
• We further demonstrate that the Hop enhancer activity is inducible ectopically in a transgenic tissue by wild-type roof plate transplantation in vitro [5].

Biological context of Hod

• Homeobox protein Hop functions in the adult cardiac conduction system [6].
• Recombinant viruses were constructed with these changes as single amino acid substitutions in a strain Toto 1101 background [2].
• RESULTS: Subtractive hybridization identified transcripts encoding Hop, a short, atypical homeodomain-containing protein that had previously been shown to be an important regulator of gene expression in the heart and lung [7].

Anatomical context of Hod

• Although lens abnormalities have yet to be identified in mice lacking Hop, the genomic sequences that regulate Hop expression in the lens may be useful for expressing exogenous transcripts selectively in fiber cells just before they fuse with their neighbors and degrade their organelles [7].

Associations of Hod with chemical compounds

• All exhibited decreased binding to heparan sulfate and had larger plaques than Toto 1101 [2].

References