Sheep neurons (red) expressing green fluroescent protein
(green) delivered by a gene therapy vector.
Dr Stephanie Hughes from the Department of Biochemistry
was recently awarded $14,400 to study the use of gene therapy
in a childhood neurodegenerative disease.
Batten disease, or neuronal ceroid lipofuscinoses (NCL), is a
group of monogenic lysosomal storage disorders characterised
by childhood blindness, seizures, dementia, progressive
decline to a vegetative state and premature death.
Ten distinct genetic loci have been identified to date with
mutations in genes encoding either soluble lysosomal proteins
or transmembrane proteins resident in either the lysosome or
the endoplasmic reticulum.
We have extensively studied two forms of these disorders in
sheep, however only recently have mutations been identified
in the sheep.
One of the sheep forms has a mutation in a gene encoding the
soluble lysosomal protein, CLN5.
The protein has no significant homology to any other protein,
nor has the function of either been established.
These sheep provide a unique resource for both studies of
protein biology and for pre-clinical testing of therapeutic
strategies.
Here, we aim to test the effects of CLN5 mutations on protein
trafficking to the lysosome and endoplasmic reticulum.
In addition the correct trafficking of wildtype CLN5 proteins
in mutant sheep neurons and the effects of gene replacement
on function of affected neurons will be tested.
These studies will provide important information on protein
trafficking and the potential for functional gene correction
in Batten disease.
This work forms part of a collaboration with Dr Hughes's and
her lab members Katie Hope and Nicole Neverman and Professor
David Palmer's group at Lincoln University.
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