A novel gene suppressed in the ventricle of carnitine-deficient juvenile visceral steatosis mice

Abstract

In order to clarify the pathogenesis and pathophysiology of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice, we performed mRNA differential display analysis with total RNA extracted from the ventricles of control and JVS mice at 14 days of age. We identified four up-regulated genes, two known and two unknown, and a novel down-regulated gene. Northern blot analysis with a novel cDNA probe derived from the down-regulated gene fragment 8A2 revealed three mRNA species of 1.1-, 1.3-, and 2.6-kb. The 1.1- and 1.3-kb mRNA species were found only in the heart, and the 2.6-kb species was found in the heart, kidney and brain, but not in skeletal muscle or liver. The 1.1- and 1.3-kb species were down-regulated in the ventricles of JVS mice, but not in the auricles, and increased to the control level with carnitine treatment. We isolated cDNA clones from ventricle RNA, termed CDV-1 (carnitine deficiency-associated gene expressed in ventricle) and from brain RNA, termed CDV-1R (CDV-1-related gene) by 5′- and 3′-RACE analyses. The entire nucleotide sequence except the 5′-terminal 64 bp of CDV-1 cDNA was completely identical to the 992 bp sequence from the 3′-end of CDV-1R cDNA. The CDV-1 cDNA contained an open reading frame predicting a peptide of 107 amino acids, which composed the C-terminal portion of CDV-1R peptide consisting of 414 amino acids.