Genetic and comparative mapping of genes dysregulated in mouse hearts lacking the Hand2 transcription factor gene

Genomics. 2002 Dec;80(6):593-600. doi: 10.1006/geno.2002.7009.


The helix-loop-helix transcription factor HAND2 plays a vital role in the development of the heart, limb, facies, and other neural crest-derived structures. We used differential display analysis to identify 33 putative HAND2-regulated ESTs that are differentially expressed in Hand2(-/-) vs wild-type mice. We determined the positions on mouse and human genetic maps of 29 of these by using the T31 mouse Radiation Hybrid panel, comparison to human genomic sequence, and comparative mapping. We examined the conserved chromosomal locations for phenotypes that involve development of heart, face, and limb structures that are affected by HAND2. One EST mapped to a region of conserved synteny between mouse chromosome 2 and human chromosome 10p. RACE analysis extended the sequence and identified this cDNA as the mouse ortholog of human nebulette, an actin-binding protein expressed in fetal heart. Nebulette was shown to be deleted in DiGeorge Syndrome 2 patients with the proximal deletion of human 10p13-p14 that is associated with cardiac and craniofacial abnormalities.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics
  • Cytoskeletal Proteins
  • Expressed Sequence Tags
  • Gene Expression Regulation
  • Humans
  • In Situ Hybridization, Fluorescence
  • LIM Domain Proteins
  • Mice
  • Muscle Proteins / genetics
  • Mutation
  • Myocardium / metabolism*
  • Phenotype
  • Radiation Hybrid Mapping
  • Synteny
  • Transcription Factors / genetics*
  • Zebrafish Proteins


  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Cytoskeletal Proteins
  • HAND2 protein, human
  • Hand2 protein, mouse
  • LIM Domain Proteins
  • Muscle Proteins
  • NEBL protein, human
  • Nebl protein, mouse
  • Transcription Factors
  • Zebrafish Proteins
  • hand2 protein, zebrafish