Biology Reference
In-Depth Information
Table 1.2. Summary of the Neurodegenerative Phenotypes Associated with the LRRK2-Related
Drosophila Models
Study
LRRK2 form
Eye phenotype
DA neuron loss
Liu
et al.
WT
þ
All clusters
G2019S
þ
All clusters
Imai
et al.
WT
N/A
0
I2020T
N/A
N/A
I1915T
N/A
PPM1/2, PPL1
Y1385C
N/A
PPM1/2, PPL1
Y1699C
N/A
N/A
dLRRK
/
N/A
0
Ng
et al.
WT
0
0
G2019S
Versus rare
(
PPM1/2, PPM3
<
1%)
Y1699C
0
PPM1/2, PPM3
G2385R
0
PPM1/2, PPM3
Venderova
et al.
WT
þþ
All clusters affected variably
under different conditions
Y1699C
þþ
I2020T
þþ
I1122V
þþ
Lee et al.
dLRRK
N/A
0
dLRRK
[¼R1441C]
N/A
0
dLRRK/
0
0
Wang et al.
dLRRK/
0
0
the same controlled conditions in one laboratory, such as was done for
-synu-
clein. For future consideration, emerging technologies such as site-specific trans-
gene integration will help circumvent some of the common technical concerns.
2. Loss-of-function models
To complement the analysis of mutated forms of human LRRK2, mirroring the
dominant inheritance pattern, and to gain an insight into the normal function of
LRRK2 homologs, a valuable approach is to analyze and perturb expression of the
endogenous gene. The Drosophila genome appears to contain a single gene that
shares significant homology to human
LRRK2
, though phylogenetic studies have
suggested that
and
appears to lack certain N-terminal repeat sequences (Marin, 2006, 2008). Never-
theless, the current state of knowledge of LRRK2 biology is very limited including
the relative contributions of the various protein domains to pathobiology; hence,
valuable understanding may still be gained from studying this ancestral gene.
dLRRK
may be somewhat distant homolog of human
LRRK2
