3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes
✍ Scribed by Shupei Wang; Joseph H. Nadeau; Alessandra Duncan; Marie-France Robert; Gisèle Fontaine; Keith Schappert; Kenneth R. Johnson; Ewa Zietkiewicz; Paul Hruz; Henry Miziorko; Grant A. Mitchell
- Publisher
- Springer-Verlag
- Year
- 1993
- Tongue
- English
- Weight
- 696 KB
- Volume
- 4
- Category
- Article
- ISSN
- 0938-8990
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✦ Synopsis
3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL) is a homodimeric mitochondrial matrix enzyme that catalyzes the last step of ketogenesis. Using a human HL cDNA as a probe, we isolated a 1.4-kb mouse HL cDNA (HLM) from a mouse liver library and extended the sequence in the 5' direction, using RACE PCR to include the complete coding sequence. The nucleotide sequence of the mouse HL coding region is 85.7% identical to human HL, and 52.6% to Ps. mevalonii HL. Peptide identities of 87.4% and 54.3% respectively were observed. Southern analysis of 29 strains of laboratory mice and of Mus spretus revealed a total of about 25 kb of hybridizing fragments and three polymorphic fragments in both EcoRI and Hin-dlII digestions. The mouse HL locus (Hmgcl) was localized on Chromosome (Chr) 4:Pmv-19-12.6 +-3.6 cM-Hmgcl-7.3 +-2.3 cM-Xmv-8-1.5 +-1.0 cM-Gpd-1. The human HL locus (HMGCL) was mapped to distal Chr lp by analysis of a human-hamster hybrid cell panel and by in situ hybridization.