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@ARTICLE{Giesert:136909,
author = {Giesert, Florian and Hofmann, Andreas and Bürger,
Alexander and Zerle, Julia and Kloos, Karina and Hafen,
Ulrich and Ernst, Luise and Zhang, Jingzhong and
Vogt-Weisenhorn, Daniela Maria and Wurst, Wolfgang},
title = {{E}xpression analysis of {L}rrk1, {L}rrk2 and {L}rrk2
splice variants in mice.},
journal = {PLOS ONE},
volume = {8},
number = {5},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DZNE-2020-03231},
pages = {e63778},
year = {2013},
abstract = {Missense mutations in the leucine-rich repeat kinase 2 gene
(LRRK2) are linked to autosomal dominant forms of
Parkinson's disease (PD). In order to get insights into the
physiological role of Lrrk2, we examined the distribution of
Lrrk2 mRNA and different splice variants in the developing
murine embryo and the adult brain of Mus musculus. To
analyse if the Lrrk2-paralog, Lrrk1, may have redundant
functions in PD-development, we also compared Lrrk1 and
Lrrk2 expression in the same tissues. Using radioactive in
situ hybridization, we found ubiquitous expression of both
genes at low level from embryonic stage E9.5 onward, which
progressively increased up until birth. The developing
central nervous system (CNS) displayed no prominent Lrrk2
mRNA signals at these time-points. However, in the entire
postnatal brain Lrrk2 became detectable, showing strongest
level in the striatum and the cortex of adult mice; Lrrk1
was only detectable in the mitral cell layer of the
olfactory bulb. Thus, due to the non-overlapping expression
patterns, a redundant function of Lrrk2 and Lrrk1 in the
pathogenesis of PD seems to be unlikely. Quantification of
Lrrk2 mRNA and protein level in several brain regions by
real-time PCR and Western blot verified the striatum and
cortex as hotspots of postnatal Lrrk2 expression. Strong
expression of Lrrk2 is mainly found in neurons, specifically
in the dopamine receptor 1 (DRD1a) and 2 (DRD2)-positive
subpopulations of the striatal medium spiny neurons.
Finally, we identified 2 new splice-variants of Lrrk2 in
RNA-samples from various adult brain regions and organs: a
variant with a skipped exon 5 and a truncated variant
terminating in an alternative exon 42a. In order to identify
the origin of these two splice variants, we also analysed
primary neural cultures independently and found
cell-specific expression patterns for these variants in
microglia and astrocytes.},
keywords = {Alternative Splicing / Animals / Brain: metabolism /
Embryonic Development: genetics / Gene Expression Profiling
/ Gene Expression Regulation, Developmental / Gene Order /
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Mice
/ Neurons: metabolism / Protein-Serine-Threonine Kinases:
genetics / Protein-Serine-Threonine Kinases: metabolism /
RNA, Messenger: genetics / RNA, Messenger: metabolism / RNA,
Messenger (NLM Chemicals) / Leucine-Rich Repeat
Serine-Threonine Protein Kinase-2 (NLM Chemicals) / Lrrk1
protein, mouse (NLM Chemicals) / Lrrk2 protein, mouse (NLM
Chemicals) / Protein-Serine-Threonine Kinases (NLM
Chemicals)},
cin = {AG Wurst},
ddc = {610},
cid = {I:(DE-2719)1140001},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23675505},
pmc = {pmc:PMC3651128},
doi = {10.1371/journal.pone.0063778},
url = {https://pub.dzne.de/record/136909},
}