Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease.

Niemann-Pick type C2 (NPC2) disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6-phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background.

Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic strains and candidate gene identification studies.

By use of newly developed subcongenic strains of mice from a parental B6.129-Il10-/- knockout/congenic strain, we have narrowed the critical region for a new behavioral QTL, called Emo4, for open-field activity to a segment of Chromosome 1 between Erbb4 (68.4Mb) and B3gnt7 (86.

Genomics of the future: identification of quantitative trait loci in the mouse.

Positional cloning of quantitative trait loci in rodents is a common approach to identify genes involved in complex phenotypes, including genes important to human disease. However, cloning the causative genes has proved to be more difficult than determining their positions. New tools such as genomic sequence, clone libraries, and new genomic-based methods offer new approaches to identify these genes.

Functional annotation of mouse mutations in embryonic stem cells by use of expression profiling.

Expression profiling offers a potential high-throughput phenotype screen for mutant mouse embryonic stem (ES) cells. We have assessed the ability of expression arrays to distinguish among heterozygous mutant ES cell lines and to accurately reflect the normal function of the mutated genes. Two ES cell lines hemizygous for overlapping regions of mouse Chromosome (Chr) 5 differed substantially from the wildtype parental line and from each other.