title: Genetic and comparative mapping of genes dysregulated in mouse hearts lacking the Hand2 transcription factor gene.
abstract: 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.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Villanueva
authors.forename: Aparna R
authors.initials: AR
authors.lastname: Aiyer
authors.forename: Shaine
authors.initials: S
authors.lastname: Muller
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Pletcher
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Beverly
authors.initials: B
authors.lastname: Emanuel
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
authors.forename: Roger H
authors.initials: RH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003598:Cytoskeletal Proteins; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D060588:LIM Domain Proteins; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D021101:Radiation Hybrid Mapping; D026801:Synteny; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C498765:HAND2 protein, human; C498766:Hand2 protein, mouse; C486890:NEBL protein, human; C486891:Nebl protein, mouse; C410915:hand2 protein, zebrafish