title: Multiple copies of the ALA-D gene are located at the Lv locus in Mus domesticus mice.
abstract: Incremental differences in delta-aminolevulinate dehydratase (ALA-D; the second enzyme of the heme biosynthetic pathway) activity among inbred mouse strains can be attributed to variation in the number of copies of the ALA-D gene. We have cloned and characterized the Lv locus from an inbred mouse strain (DBA/2J) that has three times the normal ALA-D activity levels. The entire 12-kb ALA-D gene plus 16 kb of flanking DNA are found in 28-kb tandemly repeating units. We used the derived nucleotide sequence surrounding the internal junction of the repeats to survey wild-caught mice and demonstrate that multiple copies of the ALA-D gene occur in 7 of 24 worldwide locations of Mus domesticus mice. Data are consistent with a model that high lead (Pb) in the environment may be providing a selective advantage to mice harboring multiple copies of the ALA-D gene, since the enzyme is potently inhibited by lead.
authors.affiliation: Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Bishop
authors.forename: M W
authors.initials: MW
authors.lastname: Miller
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: P M
authors.initials: PM
authors.lastname: Dierks
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003360:Cosmids / Q000302:isolation & purification; D018628:Gene Dosage; D007982:Levulinic Acids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D005810:Multigene Family; D000623:Porphobilinogen Synthase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D007982:Levulinic Acids; D000623:Porphobilinogen Synthase; C032246:levulinic acid