Towards humane end points: behavioural changes precede clinical signs of disease in a Huntington's disease model.

The number of animals used in science is increasing, bringing a concomitant obligation to minimize suffering. For animals with progressive conditions, euthanasia at a 'humane end point' is advised if the end point is scientifically valid, predictive and accurate. Our aim was to test the hypothesis that behavioural changes would reliably precede clinical signs of disease in a progressive neurological model, using retrospective analysis.

Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice.

The pulmonary adenoma susceptibility 1 (Pas1) locus affects inherited predisposition and resistance to chemically induced lung tumorigenesis in mice. The A/J and C57BL/6J mouse strains carry the susceptibility and resistance allele, respectively. We identified and genotyped 65 polymorphisms in the Pas1 locus region in 29 mouse inbred strains, and delimited the Pas1 locus to a minimal region of 468 kb containing six genes.

Effects of dopaminergic cell degeneration on electrophysiological characteristics and GAD65/GAD67 expression in the substantia nigra: different action on GABA cell subpopulations.

The motor disturbances occurring in Parkinson's disease have been partially attributed to a hyperactivity of gamma-aminobutyric acid (GABA)-ergic nigral cells largely in the substantia nigra pars reticulata (SNr) secondary to the degeneration of dopaminergic nigrostriatal neurons. However, some aspects of this response remain unclear. In this work, different electrophysiological and neurochemical parameters were studied in GABAergic cells of the SN after unilateral nigrostriatal dopaminergic lesion using 6-hydroxydopamine injection in rats.

A new locus for resistance to gamma-radiation-induced thymic lymphoma identified using inter-specific consomic and inter-specific recombinant congenic strains of mice.

Mice of the C57BL/6J inbred strain develop thymic lymphomas at very high frequency after acute gamma-irradiation, while mice of several inbred strains derived from the wild progenitor of the Mus spretus species and their F1 hybrids with C57BL/6J appear extremely resistant. Analysis of the genetic determinism of the gamma-radiation-induced thymic lymphoma (RITL) resistance with the help of inter-specific consomic strains (ICS), which carry a single introgressed Mus spretus chromosome on a C57BL/6J genetic background, provide significant evidence for the existence of a thymic lymphoma resistance (Tlyr1) locus on chromosome 19. The subsequent analysis of the backcross progeny resulting from a cross between consomic mice heterozygous for the Mus spretus chromosome 19 and C57BL/6J mice, together with the study of inter-specific recombinant congenic strains (IRCS), suggest that this Tlyr1 locus maps within the D19Mit60-D19Mit40 chromosome interval.

Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains.

Lung tumor susceptibility in inbred mouse strains is caused by the susceptibility allele at the pulmonary adenoma susceptibility 1 (Pas1(s)) locus. However, after urethane treatment, most strains carrying the Pas1(s) allele show an intermediate (1-4 tumors/mouse) instead of a highly susceptible (15-30 tumors/mouse) lung tumor phenotype. To test the hypothesis that strains displaying the intermediate lung tumor phenotype carry dominant or codominant resistance alleles at pulmonary adenoma resistance (Par) loci, we crossed mice of intermediate susceptibility or resistance to lung tumorigenesis with the highly susceptible A/J strain.