A locus for circadian period of locomotor activity on mouse proximal chromosome 3.
Lengthened circadian period of locomotor activity is a characteristic of a congenic strain of mice carrying a nonsense mutation in exon 5 of the carbonic anhydrase II gene, car2. The null mutation in car2 is located on a DBA/2J inbred strain insert on proximal chromosome 3, on an otherwise C57BL/6J genomic background. Since reducing the size of the congenic region would narrow the possible candidate genes for period, two recombinant congenic strains (R1 and R2) were developed from the original congenic strain. These new congenic strains were assessed for period, genetic composition, and the presence of immunoreactive carbonic anhydrase II. R1 mice were homozygous DBA/2J for the distal portion of the original DBA/2J insert, while R2 mice were homozygous DBA/2J for the proximal portion. R1 mice had a significantly lengthened period compared to R2 mice and wild-type C57BL/6J mice, indicating that the gene(s) affecting period is likely found within the reduced DBA/2J insert (approximately 1 cM) in the R1 mice. The R1 mice also possessed the null mutation in car2. This study confirmed the presence of a gene(s) affecting period on proximal chromosome 3 and significantly reduced the size of the congenic region and the number of candidate genes. Future studies will focus on identifying the gene influencing period.
Program in Medical Neurobiology, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. amayeda@iupui.edu
Kari L
KL
Kernek
James A
JA
Trofatter
Aimee R
AR
Mayeda
John R
JR
Hofstetter
D000818:Animals; D020296:Animals, Congenic; D001483:Base Sequence; D024402:Carbonic Anhydrase II / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D005260:Female; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics* / Q000502:physiology
D018389:Codon, Nonsense; D004247:DNA; D024402:Carbonic Anhydrase II