Batten disease

Human Genome Research

Investigators

Abstract

We have created a mouse carrying a deletion of the Cln3 gene which encodes a transmembrane lysosomal protein of unknown function. The mouse has the same biochemical abnormalities seen in human patients with Batten disease. Work in yeast performed at University of Rochester has revealed that the yeast ortholog of Cln3 is a vacuolar protein which, when deficient, abnormally lowers the vacuolar pH. We hypothesized that humans (and mice) deficient in Cln3 might store lipofuschin in their lysosomes because of abnormal depression of lysosomal pH that interferes with degradative enzyme function. We have started a treatment protocol of mice with chloroquine, an alkaline base that accumulates in the lysosome, to see if we can correct the biochemical abnormalities seen in Batten disease with this widely used and characterized drug.