Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Molecular cloning, chromosomal mapping, and characterization of the human cardiac-specific homeobox gene hCsx.
Turbay D
,
Wechsler SB
,
Blanchard KM
,
Izumo S
.
???displayArticle.abstract???
BACKGROUND: Csx/Nkx2.5, a murine nonclustered homeobox gene expressed primarily in the heart, has significant sequence similarity to the Drosophila tinman gene. Tinman is essential for heart and gut formation in Drosophila. Targeted mutation in the mouse gene, Csx/Nkx2.5, arrests cardiac development during early embryonic stages, suggesting an evolutionary conservation in cardiogenesis.
MATERIALS AND METHODS: We have isolated and characterized a human homolog, hCsx, from an adult cardiac cDNA library. Northern blotting and ribonuclease protection was used to define the pattern of expression during normal development and in disease states. Chromosomal localization of the gene was determined by somatic cell hybrid analysis and fluorescent in situ hybridization.
RESULTS: The predicted amino acid sequence of hCsx has 87% overall homology to the murine gene with 100% identity in the homeodomain. The homeodomain sequence of hCsx is 95% identical to its Xenopus homolog, and 65% to tinman. hCsx mRNA was detected exclusively in the heart. hCsx transcript was detected at 12 weeks in human embryonic heart, the earliest time point examined, and was up-regulated 5-fold between 12 and 19 weeks. There was no significant alteration of hCsx message level in the myocardium of 14 patients with end stage heart failure compared to a normal control. The human gene mapped to the distal portion of chromosome 5, the 5q34-q35 region. This defines a new synteny region between human chromosome 5q and the t-locus of mouse chromosome 17, where the mouse Csx gene is located.
CONCLUSIONS: hCsx, the human homolog of Drosophila tinman, is expressed in heart in a tissue restricted manner. Distal 5q trisomies produce several phenotypic abnormalities, including a high incidence of congenital heart disease. Isolation of the hCsx gene will allow further studies of mutations in this gene and their potential associations with some forms of congenital heart disease in humans.
Azpiazu,
tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila.
1993, Pubmed
Azpiazu,
tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila.
1993,
Pubmed
Bodmer,
The gene tinman is required for specification of the heart and visceral muscles in Drosophila.
1993,
Pubmed
Bodmer,
A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila.
1990,
Pubmed
Bouvagnet,
Deciphering the molecular genetics of congenital heart disease.
1994,
Pubmed
Byrne,
Morphology of early fetal deaths and their chromosomal characteristics.
1985,
Pubmed
Church,
Genomic sequencing.
1984,
Pubmed
Dietz,
Molecular genetic approaches to the study of human cardiovascular disease.
1994,
Pubmed
Dohrmann,
A new Drosophila homeo box gene is expressed in mesodermal precursor cells of distinct muscles during embryogenesis.
1990,
Pubmed
Edmondson,
Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis.
1994,
Pubmed
Forejt,
Mouse chromosome 17.
1994,
Pubmed
Fryns,
Cytogenetic survey in couples with recurrent fetal wastage.
1984,
Pubmed
Gehring,
Homeodomain-DNA recognition.
1994,
Pubmed
Gehring,
Homeodomain proteins.
1994,
Pubmed
Heikinheimo,
Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development.
1994,
Pubmed
Himmelbauer,
High-resolution genetic analysis of a deletion on mouse chromosome 17 extending over the fused, tufted, and homeobox Nkx2-5 loci.
1994,
Pubmed
,
Xenbase
Kenny,
Changes in intracardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fetus: a prospective Doppler echocardiographic study.
1986,
Pubmed
Kim,
Drosophila NK-homeobox genes.
1989,
Pubmed
Komuro,
Csx: a murine homeobox-containing gene specifically expressed in the developing heart.
1993,
Pubmed
Kozak,
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
1987,
Pubmed
Lints,
Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants.
1993,
Pubmed
Lyon,
Derivation of mutant t-haplotypes of the mouse by presumed duplication or deletion.
1977,
Pubmed
Lyons,
Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.
1995,
Pubmed
McDonald,
Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma.
1994,
Pubmed
Nora,
Causes of congenital heart diseases: old and new modes, mechanisms, and models.
1993,
Pubmed
Pierce,
A positive selection vector for cloning high molecular weight DNA by the bacteriophage P1 system: improved cloning efficacy.
1992,
Pubmed
Price,
Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain.
1992,
Pubmed
Rudnicki,
MyoD or Myf-5 is required for the formation of skeletal muscle.
1993,
Pubmed
St John Sutton,
Quantitative assessment of growth and function of the cardiac chambers in the normal human fetus: a prospective longitudinal echocardiographic study.
1984,
Pubmed
St John Sutton,
Quantitative assessment of right and left ventricular growth in the human fetal heart: a pathoanatomic study.
1984,
Pubmed
Tamkun,
Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle.
1991,
Pubmed
Tonissen,
XNkx-2.5, a Xenopus gene related to Nkx-2.5 and tinman: evidence for a conserved role in cardiac development.
1994,
Pubmed
,
Xenbase
Wechsler,
Localization of the human Mxi1 transcription factor gene (MXI1) to chromosome 10q24-q25.
1994,
Pubmed
Weintraub,
The myoD gene family: nodal point during specification of the muscle cell lineage.
1991,
Pubmed
Zavala,
Isolated congenital heart defects in first degree relatives of 185 affected children. Prospective study in Mexico City.
1992,
Pubmed
