title: A single copy of carbonic anhydrase 2 restores wild-type circadian period to carbonic anhydrase II-deficient mice.
abstract: Carbonic anhydrase II (CA-II)-deficient mice have long circadian periods compared to their siblings with normal CA-II levels. The CA-II-deficient mice differ genetically from their siblings at proximal chromosome three, where the mutated carbonic anhydrase 2 gene sits on a small insert of DNA from the DBA/2J strain. The rest of the genome is that of the C57BL/6J strain. The goal of this study was to test the hypothesis that the null mutation in carbonic anhydrase 2 and the long circadian period phenotype were linked. In order to separate the effect of the null mutation in carbonic anhydrase 2 from the effect of DBA/2J alleles of other genes on the insert, two new lines of mice were studied. The first line, Kar, was developed from a CA-II-deficient mouse that had a fortuitous recombination restoring functional CA-II without affecting the rest of the DBA/2J insert. The second line was generated by breeding DBA/2J mice and C57BL/6J mice until they had the genomic composition of CA-II-deficient mice without the null mutation. Both lines of mice had circadian periods not different from C57BL/6J mice and shorter than CA-II-deficient mice. The phenotype of the new lines showed that the long circadian period characteristic of the CA-II-deficient mice arises when functional CA-II is absent, not when DBA/2J alleles are present on proximal chromosome three.
authors.affiliation: Program in Medical Neurobiology, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, 46202, USA.
authors.forename: Kari L
authors.initials: KL
authors.lastname: Kernek
authors.forename: James A
authors.initials: JA
authors.lastname: Trofatter
authors.forename: Aimee R
authors.initials: AR
authors.lastname: Mayeda
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
authors.forename: John R
authors.initials: JR
authors.lastname: Hofstetter
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D024402:Carbonic Anhydrase II / Q000172:deficiency* / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D007438:Introns / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D010641:Phenotype; D011995:Recombination, Genetic / Q000235:genetics
chemical_list: D024402:Carbonic Anhydrase II