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Table 2 Neuronal phenotype of autophagy related knockout/knockdown animal models.

From: All-you-can-eat: autophagy in neurodegeneration and neuroprotection

Protein function Knockout/knockdown OE/TG ES/M @ IMSR Neuronal phenotype after k.o./k.d.
(Animal model)
K.o. embryonic lethal
Ser/Thr protein kinase (regulation and vesicle formation) [107, 112, 113] *
[97, 99, 100, 131, 132, 135, 141, 145]
[140] (OE) ES
M (GT)
Impaired endocytosis of nerve growth factor, excessive axon arborization, stunted axon elongation (MM)
Paralysis, aberrant axon growth, abnormal vesicles, arrested differentiation (CE)
Yes (DM)
ATG3 Ubiquitin-conjugating-like enzyme (attaches MAP1LC3 to PE) [111, 143]   n.a. Not reported Yes (DM)
ATG4 Cystein protease (cleaves C-terminus of MAP1LC3 for conjugation) [90, 144]   ES
Not reported Yes (CE)
ATG5 Unknown (conjugates to ATG12, binds ATG16) [60] *
[91, 130, 141]
Progressive motor deficits, accumulation of inclusion bodies, neurodegeneration, aberrant vacuoles in Purkinje cells (MM) No # (DM/MM)
Unknown (part of class III PI3K complex, anchor protein, autophagy initiation) [59] *
[97, 116, 124, 137, 146]
[119] (TG) M (TG) Neurodegeneration, lysosomal abnormalities (MM) Yes (MM/CE/DM)
Class III PI3K complex (forms complex with BECN1/PIK3R4/AMBRA1/UVRAG, autophagy initiation) [123, 142] *
[114, 126]
  ES Abnormal protein aggregation, abnormal locomotion (CE) Yes (CE)
(VPS15, P150)
Ser/Thr protein kinase (forms a complex with and activates PIK3C3) [134]   ES Not reported Yes (DM)
AMBRA1 Unknown (component of the class III PI3K complex) [83] *   ES Neural tube defects, polyU aggregates, unbalanced cell proliferation, cell death (MM) Yes (MM)
ATG7 Ubiquitin-activating-like enzyme (activates MAP1LC3 and ATG12 for conjugation) [61, 123, 129] *
[124, 125, 127, 128, 136, 141]
  ES Behavioral deficits, neuronal loss, polyU inclusions, axonal dystrophy, axonal terminal degeneration (MM)
PolyU aggregates, neuronal degeneration (DM)
Abnormal protein aggregation (CE)
No # (DM/MM)
Unknown (similarity with ubiquitin, part of autophagosomal membrane) [123, 145] *
[79, 97]
[27] (TG) ES
M (TG)
Abnormal protein aggregation (CE) Yes (CE)
No (MM)
ATG12 Unknown (similarity with ubiquitin, conjugated to ATG5) [123] *   n.a. Abnormal protein aggregation (CE) Unknown
Unknown (part of the ESCRT-III complex, involved in surface receptor degradation, formation of MVBs and autophagosomes) [85, 115, 138]   ES Dendritic and axonal branching impaired, dendritic retraction, reduced cell viability, autophagosomes accumulate, increased htt toxicity (DM) Yes (MM)
Chaperone (recognizes CMA motif, lysosomal translocation) [121, 139] * [120] (OE) ES Impaired transmitter release, o.e. rescues α-synuclein pathology, Bolwig's nerve projection abnormalities (DM) Yes (DM)
LAMP2 Unknown (Lysosomal membrane glyco-protein, forms complex with HSPA8) [40]   ES Not reported No (MM)
  1. Examples of model organism with knockout, knockdown, or overexpression of autophagy genes and the corresponding neuronal phenotype. Approved human gene names are used, in addition commonly used aliases are provided. # While non-neuronal Atg5 and Atg7 k.o. mice survive birth, they die within one day postnatal. (MM): M. musculus; (DM): D. melanogaster; (CE): C. elegans; (OE): overexpression; (ES): embryonic knockout stem cell; (M): mouse line; (TG): transgenic; (GT): gene-trap; (MUT): targeted mutation; (IMSR): knockout ES/mice available through the International Mouse Strain Resource; (*): neuronal tissue examined; (n.a.): not available.