The Biology of Batten Disease

The Davidson laboratory studies inherited genetic diseases that cause central nervous system dysfunction and gene therapy to the central nervous system. One form of Batten disease, a childhood onset neurodegerative disease, is due to a deficiency of a lysosomal protein, ceroid lipofuscinosis type III, or CLN3. We showed that CLN3 is a lysosomal membrane protein (1) and also how mutations within CLN3 alter protein trafficking and function (2,3). Using in vitro transcription and translation experiments, we have begun to unravel how the protein orientates itself within the lysosomal membrane (4). Additional experiments are underway to test if CLN3 associates with other lysosomal or non-lysosomal proteins. With the CLN3 animal model in hand, we are also determining if gene transfer of CLN3 to the brain restores neuron survival. The ultimate goal is to understand how an absence of CLN3 leads to neurodegeneration, and to test if gene replacement imparts protection to the degenerative phenotype.

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References:

1. RE Haskell et al. Mol Gen & Metab 66:253-260, 1999.
2. RE Haskell et al. Hum Mol Genet 9(5):735-744, 2000.
3. Q Mao et al. FEBS lett 541:40-46, 2003.
4. Q Mao et al. FEBS lett 555:351-357, 2003.