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. (C) 2002 Elsevier Science B.V. All rights reserved.