A Drosophila model of neuronal ceroid lipofuscinosis CLN4 reveals a hypermorphic gain of function mechanism.
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ABSTRACT:
SUBMITTER: Imler E
PROVIDER: S-EPMC6897512 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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A <i>Drosophila</i> model of neuronal ceroid lipofuscinosis <i>CLN4</i> reveals a hypermorphic gain of function mechanism.
Imler Elliot E Pyon Jin Sang JS Kindelay Selina S Torvund Meaghan M Zhang Yong-Quan YQ Chandra Sreeganga S SS Zinsmaier Konrad E KE
eLife 20191030
The autosomal dominant neuronal ceroid lipofuscinoses (NCL) <i>CLN4</i> is caused by mutations in the synaptic vesicle (SV) protein CSPα. We developed animal models of <i>CLN4</i> by expressing <i>CLN4</i> mutant human CSPα (hCSPα) in <i>Drosophila</i> neurons. Similar to patients, <i>CLN4</i> mutations induced excessive oligomerization of hCSPα and premature lethality in a dose-dependent manner. Instead of being localized to SVs, most <i>CLN4</i> mutant hCSPα accumulated abnormally, and co-loca ...[more]
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