A single copy of carbonic anhydrase 2 restores wild-type circadian period to carbonic anhydrase II-deficient mice.

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.

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.

New quantitative trait loci for the genetic variance in circadian period of locomotor activity between inbred strains of mice.

Provisional quantitative trait loci (QTL) for circadian locomotor period and wheel-running period have been identified in recombinant inbred (RI) mouse strains. To confirm those QTL and identify new ones, the genetic component of variance of the circadian period was partitioned among an F2 intercross of RI mouse strains (BXD19 and CXB07). First, a genomic survey using 108 SSLP markers with an average spacing of 15 cM was carried out in a population of 259 (BXD19 x CXB07)F2 animals.

A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.

Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia.

Cloning and characterization of a novel human clathrin heavy chain gene (CLTCL).

An exon representing a novel clathrin heavy chain gene (CLTCL) was isolated during gene identification studies and transcription mapping of human chromosome 22. Isolation and sequencing of cDNA clones corresponding to this exon revealed extensive similarity of the predicted amino acid sequence of this gene product to those of clathrin heavy chain genes of other species. Northern blot analysis has revealed an apparent developmental expression pattern of an approximately 6-kb mRNA.