PMID- 16408247 OWN - NLM STAT- MEDLINE DCOM- 20061011 LR - 20061115 IS - 0001-8244 (Print) IS - 0001-8244 (Linking) VI - 36 IP - 2 DP - 2006 Mar TI - A single copy of carbonic anhydrase 2 restores wild-type circadian period to carbonic anhydrase II-deficient mice. PG - 301-8 AB - 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. FAU - Kernek, Kari L AU - Kernek KL AD - Program in Medical Neurobiology, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, 46202, USA. FAU - Trofatter, James A AU - Trofatter JA FAU - Mayeda, Aimee R AU - Mayeda AR FAU - Lahiri, Debomoy K AU - Lahiri DK FAU - Hofstetter, John R AU - Hofstetter JR LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20060112 PL - United States TA - Behav Genet JT - Behavior genetics JID - 0251711 RN - EC 4.2.1.- (Carbonic Anhydrase II) SB - IM MH - Alleles MH - Animals MH - Base Sequence/genetics MH - Carbonic Anhydrase II/*deficiency/*genetics MH - Chromosomes, Mammalian/genetics MH - Circadian Rhythm/*genetics MH - Exons/genetics MH - Heterozygote MH - Homozygote MH - Introns/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred DBA MH - Models, Genetic MH - Mutagenesis, Insertional MH - Phenotype MH - Recombination, Genetic/genetics EDAT- 2006/01/13 09:00 MHDA- 2006/10/13 09:00 CRDT- 2006/01/13 09:00 PHST- 2005/04/20 00:00 [received] PHST- 2005/07/14 00:00 [accepted] PHST- 2006/01/13 09:00 [pubmed] PHST- 2006/10/13 09:00 [medline] PHST- 2006/01/13 09:00 [entrez] AID - 10.1007/s10519-005-9032-9 [doi] PST - ppublish SO - Behav Genet. 2006 Mar;36(2):301-8. doi: 10.1007/s10519-005-9032-9. Epub 2006 Jan 12.