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Ultrafine mapping of Dyscalc1 to an 80-kb chromosomal segment on chromosome 7 in mice susceptible for dystrophic calcification.
Aherrahrou, Zouhair; Doehring, Lars C; Kaczmarek, Piotr M; Liptau, Henrike; Ehlers, Eva-Maria; Pomarino, Andrea; Wrobel, Sandra; Götz, Anika; Mayer, Bjoern; Erdmann, Jeanette; Schunkert, Heribert.
Afiliación
  • Aherrahrou Z; Medizinische Klinik II, University of Luebeck, Luebeck, Germany. aherrazou@o2online.de
Physiol Genomics ; 28(2): 203-12, 2007 Jan 17.
Article en En | MEDLINE | ID: mdl-16926270
ABSTRACT
In mice, dystrophic cardiovascular calcification (DCC) is controlled by a major locus on proximal mouse chromosome 7 named Dyscalc1. Here we present a strategy that combines in silico analysis, expression analysis, and extensive sequencing for ultrafine mapping of the Dyscalc1 locus. We subjected 15 laboratory mouse strains to freeze-thaw injury of the heart, and association with respective genotypes allowed condensation of the Dyscalc1 locus to 1 Mb. Within this region, 51 known and predicted genes were studied in DCC-susceptible C3H/He and DCC-resistant C57BL/6 mice with respect to mRNA expression in response to injury. Five genes displayed differential expression. Genotyping of seven novel single nucleotide polymorphisms (SNPs) within these genes revealed an 80-Kb region in NZB mice that were found positive for calcification though carrying otherwise alleles from DCC-resistant mice. This microheterogeneity in NZB mice was evolutionary conserved in all DCC-susceptible mouse strains and contains the genes EMP-3, BC013491, and Abcc6 (partially). The flanking SNPs are rs3703247 and NT_039420.5_2757991. mRNA levels of EMP-3 were found to be upregulated in response to injury in both C57BL/6 and C3H/He mice. Sequencing of EMP-3 revealed an SNP leading to an amino acid substitution (p.T153I) that was found in all mouse strains susceptible for DCC but not in resistant strains such as C57BL/6 mice. Thus, the p.T153I changes might affect the biological function of EMP-3 gene product after injury. Using this combined approach, we ultrafine-mapped the Dyscalc1 locus to an 80-Kb region and identified EMP-3 as a new candidate gene for DCC.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcinosis / Mapeo Cromosómico / Cromosomas de los Mamíferos / Cardiomiopatías Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Physiol Genomics Asunto de la revista: BIOLOGIA MOLECULAR Año: 2007 Tipo del documento: Article País de afiliación: Alemania
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcinosis / Mapeo Cromosómico / Cromosomas de los Mamíferos / Cardiomiopatías Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Physiol Genomics Asunto de la revista: BIOLOGIA MOLECULAR Año: 2007 Tipo del documento: Article País de afiliación: Alemania