cDNA cloning, mapping and expression of the mouse Propionyl CoA Carboxylase Beta (pccb), the gene for human type II propionic acidaemia

Propionyl CoA carboxylase (PCC) is a mitochondrial, biotin-dependent enzyme involved in the catabolism of amino acids, odd-chained fatty acids and oth er metabolites. PCC is composed of two equal subunits, alpha and beta, whic h are encoded by two separate genes at two distinct human loci. Mutations o f either gene in humans results in propionic acidemia (PA). To identify the mouse cDNA for the propionyl CoA carboxylase beta -subunit (pccb), we have screened the mouse EST database using the human sequence. The murine mRNA transcript is similar to2.3 kb, nearly 500 bps larger than the human simila r to1.8 kb transcript. A PAC genomic DNA clone from the mouse was also isol ated and used to generate probes and PCR primers for mapping the pccb locus in the mouse. Both the C57B1/6JEi and Spret/Ei alleles for regions flankin g the pccb gene were sequenced to identify RFLPs. The Jackson Laboratory BS S and BSB backcross panel DNAs were then analyzed using a DdeI polymorphism placing the pccb locus on mouse chromosome 9, Northern blots of adult tiss ue show that the pccb gene is broadly expressed in the mouse. The similar t o2.3 kb transcript is most abundantly expressed in the kidney, liver, small intestine and stomach tissues. (C) 2001 Elsevier Science B.V. All rights r eserved.