TY  - JOUR
A1  - Mirza, Myriam
A1  - Vainshtein, Anna
A1  - DiRonza, Alberto
A1  - Chandrachud, Uma
A1  - Haslett, Luke J.
A1  - Palmieri, Michela
A1  - Storch, Stephan
A1  - Groh, Janos
A1  - Dobzinski, Niv
A1  - Napolitano, Gennaro
A1  - Schmidtke, Carolin
A1  - Kerkovich, Danielle M.
T1  - The CLN3 gene and protein: What we know
JF  - Molecular Genetics & Genomic Medicine
N2  - Background
One of the most important steps taken by Beyond Batten Disease Foundation in our quest to cure juvenile Batten (CLN3) disease is to understand the State of the Science. We believe that a strong understanding of where we are in our experimental understanding of the CLN3 gene, its regulation, gene product, protein structure, tissue distribution, biomarker use, and pathological responses to its deficiency, lays the groundwork for determining therapeutic action plans.

Objectives
To present an unbiased comprehensive reference tool of the experimental understanding of the CLN3 gene and gene product of the same name.

Methods
BBDF compiled all of the available CLN3 gene and protein data from biological databases, repositories of federally and privately funded projects, patent and trademark offices, science and technology journals, industrial drug and pipeline reports as well as clinical trial reports and with painstaking precision, validated the information together with experts in Batten disease, lysosomal storage disease, lysosome/endosome biology.

Results
The finished product is an indexed review of the CLN3 gene and protein which is not limited in page size or number of references, references all available primary experiments, and does not draw conclusions for the reader.

Conclusions
Revisiting the experimental history of a target gene and its product ensures that inaccuracies and contradictions come to light, long-held beliefs and assumptions continue to be challenged, and information that was previously deemed inconsequential gets a second look. Compiling the information into one manuscript with all appropriate primary references provides quick clues to which studies have been completed under which conditions and what information has been reported. This compendium does not seek to replace original articles or subtopic reviews but provides an historical roadmap to completed works.
KW  - Batten
KW  - CLN3
KW  - JNCL
KW  - juvenile Batten
KW  - neuronal ceroid lipofuscinosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224138
VL  - 7
ER  - 
TY  - JOUR
A1  - Grünewald, Benedikt
A1  - Lange, Maren D
A1  - Werner, Christian
A1  - O'Leary, Aet
A1  - Weishaupt, Andreas
A1  - Popp, Sandy
A1  - Pearce, David A
A1  - Wiendl, Heinz
A1  - Reif, Andreas
A1  - Pape, Hans C
A1  - Toyka, Klaus V
A1  - Sommer, Claudia
A1  - Geis, Christian
T1  - Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis
JF  - eLife
N2  - Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3\(^{Δex1-6}\)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
KW  - CLN3
KW  - mutation
KW  - mouse model
KW  - synaptic transmission
KW  - amygdala
KW  - hippocampus
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170004
VL  - 6
IS  - e28685
ER  -