Biomedical subjects

K Duff

Publications and source records attributed to K Duff.

60 records · Page 4Linked to original sources

PubMed1992

A locus for familial early-onset Alzheimer's disease on the long arm of chromosome 14, proximal to the alpha 1-antichymotrypsin gene.

Although mutations in the beta-amyloid precursor protein gene (APP) on chromosome 21 cause some cases of early-onset Alzheimer's disease (AD), most cases evidently do not have mutations in APP. We analysed ten early-onset families for linkage to APP and markers elsewhere in the genome. One family (F172) was consistent with linkage to chromosome 21 and was subsequently found to have an APP Val to Ile mutation. Of the others, all but one were consistent with linkage to markers in the middle long arm of chromosome 14. However, no family showed independent evidence of linkage with two point analysis and only one showed independent evidence of linkage on multipoint analysis. Therefore, we cannot rule out heterogeneity at these loci although tests for heterogeneity were not significant.

Adult↗

PubMed1992

Secondary structure analysis identifies a putative mouse protein demonstrating similarity to the repeat units found in CDC4, the G protein beta subunits and related proteins.

The predicted protein product of an anonymous clone isolated from a cDNA library prepared from 12 day post coitum (p.c) embryonic mouse heart tissue demonstrated the same segmental repeats previously identified in the cell division control protein, CDC4 and the G protein beta 1 subunit. A search of the protein database subsequently identified three other classes of protein containing the repeat. Secondary structure analyses performed on the repeat sequences revealed a high degree of conservation suggesting that the repeat motif performs a specific function in a diverse range of proteins.

Amino Acid Sequence↗

PubMed1990

Expression of genes encoding two chains of the collagen type VI molecule during human fetal heart development.

Northern blot analysis was used to demonstrate the expression of genes encoding two chains of the extracellular matrix molecule, collagen type VI, in human fetal heart tissue. Both genes have been mapped to the Down's obligate region of chromosome 21. As congenital heart malformations are a common feature of Down's syndrome, developmentally regulated structural protein genes encoded by chromosome 21 are being investigated.

Blotting, Northern↗

PubMedDate not supplied

A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease.

Vaccinations with amyloid-beta peptide (A beta) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease. To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A beta vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates. Here we show that vaccination with A beta protects transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer's disease. During testing for potential deleterious effects of the vaccine, all mice performed superbly on the radial-arm water-maze test of working memory. Later, at an age when untreated transgenic mice show memory deficits, the A beta-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The A beta-vaccinated mice also had a partial reduction in amyloid burden at the end of the study. This therapeutic approach may thus prevent and, possibly, treat Alzheimer's dementia.

Aging↗

PubMedDate not supplied

Exclusion mapping in familial non-specific dementia.

We present genetic linkage data in a large family in which non-specific dementia is inherited as an autosomal dominant trait. We have analyzed 45 highly polymorphic microsatellite sequences and excluded a quarter of the genome as the site of the pathogenic mutation in this family.

Adult↗

PubMedDate not supplied

Mice transgenic for a human amyloid precursor protein promoter-lacZ reporter construct.

Transgenic mouse lines were generated that expressed a 2-kb amyloid precursor protein (APP) promoter/beta-galactosidase reporter gene construction. In brain, hippocampal pyramidal neurons, neurons in the deeper layers of cerebral cortex, and neurons in several thalamic nuclei were heavily labeled by beta-galactosidase histochemistry. In general, molecular layers and white matter regions did not express the reporter gene. When compared with in situ hybridization for endogenous murine APP RNA, the striatum and outer layers of cerebral cortex had little reporter expression. Thus, the match between reporter expression and endogenous APP expression in brain was not perfect. A similar mismatch between the relative expression of the reporter gene and endogenous APP RNA distribution was found in homogenates from several organs. Although prior work in transgenic mice found similar mismatches in reporter gene distribution, none had tested the APP promoter construct in response to neuronal injury. Kainic acid injections successfully increased murine APP expression in the transgenic mice, but had no effect on the reporter gene expression. Based on these data and those collected by others, we conclude that the 2-kb region upstream of the APP transcription initiation site contains some elements responsible for the tissue-specific expression of this gene, but does not contain all the cis-acting elements sufficient for either the differential tissue distribution of this gene or the regulation of this gene subsequent to neural damage.

Amyloid beta-Protein Precursor↗