Novel mRNA molecules are induced in hypertrophied ventricles of carnitine-deficient mice and belong to a family of up-regulated gene in cells overexpressing c-erbB-2.
To clarify the pathogenesis of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice, we performed differential mRNA display analysis with the ventricles of control and JVS mice. We found a novel up-regulated gene, designated as carnitine deficiency-associated gene expressed in ventricle (CDV)-3. Northern blot analysis with a cDNA probe derived from the novel gene revealed two substantial mRNA species of prominent 4.1- and faint 3.5-kb in examined tissues of control and JVS mice. In spite of their widely expressed features, up-regulation of the gene was found predominantly in the ventricles and slightly in the auricles and skeletal muscles of JVS mice. The up-regulation of CDV-3 gene in the ventricles of JVS mice was significantly relieved by carnitine administration within 6 h. The entire cDNA nucleotide sequences showed that two kinds of cDNA, long and short versions (CDV-3A and -3B), corresponding to the detected mRNAs, are different in a 711 base fragment. Analysis of genomic DNA revealed that the two mRNAs were derived from a single CDV-3 gene with five exons by alternative splicing. The deduced amino acid sequences indicated that the isoforms consist of 236 and 281 residues, differing at regions near the carboxy-terminus but sharing 231 residues of the amino-terminal regions. A BLAST search revealed that they show a high similarity to a human predicted nuclear protein (H41), which has been reported to be up-regulated in breast cancer cells overexpressing cellular-erythroblastosis B-2 (c-erbB-2, a kind of tyrosine kinase).We report the identification and characterization of novel transcripts that may be involved in the development of cardiac hypertrophy caused by carnitine deficiency.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D002331:Carnitine / Q000172:deficiency*; D003001:Cloning, Molecular; D005091:Exons; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D006352:Heart Ventricles; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*
D012333:RNA, Messenger; D002331:Carnitine