ULK1 complex
|
Ulk1
|
ulk1-/-
|
Viable; no developmental defects or impairment to starvation-induced autophagy; delayed mitochondria elimination from reticulocytes
|
168
|
Ulk2
|
ulk2-/-
|
Viable; no overt phenotype/fertility defects
|
169
|
ulk1-/-; ulk2-/-
|
Neonatal lethal; impaired response to amino acid deprivation
|
Rb1cc1
|
rb1cc1-/-
|
Embryonic lethal at E14.5-15.5; excessive liver and cardiac apoptosis; thin left ventricular wall, lacking trabeculation
|
170-172
|
Tek-Cre; Rb1cc1fl/fl
|
Perinatal lethal; severe erythroblastic anemia; 6-fold decrease in HSCs; increased number of myeloid cells in liver
|
173-175
|
Atg13
|
|
Currently no KO mouse
|
|
C12orf44
|
|
Currently no KO mouse
|
PtdIns3K complex
|
Ambra1
|
ambra1-/-
|
Non-viable; embryos show neural tube defects, spina bifida at E10-E14.5, accumulation of ubiquitinated proteins, and increased apoptosis in various tissues
|
177
|
Becn1
|
becn1-/-
|
Embryonic lethal at E7.5; failure to close pro-amniotic canal
|
183
|
Becn1+/-
|
Increased tumor incidence in various tissues
|
184
|
becn1-/-; rag1-/-
|
Reduced levels of early marrow-derived thymocytes and B cells
|
185
|
PtdIns3k
|
Meox1-Cre; Pik3c3fl/fl
|
Embryonic lethal at E7.5; embryos fail to form recognizable mesoderm
|
187
|
Alb-Cre; Pik3c3fl/fl
|
Smaller adult mice; enlarged, pale liver. In hepatocytes: Reduced levels of autophagy nucleation complex; arrested autophagic flux; increased intracellular lipid droplet formation; reduced size of mitochondria
|
188
|
Ckm-Cre; Pik3c3fl/fl
|
Lethal between 5-13 weeks; Cardiomegaly with increased thickness of left ventricular wall, decreased cardiac contractility/reduced cardiac output; arrested autophagic flux; Reduced size of mitochondria
|
188
|
Uvrag
|
|
Currently no KO mouse
|
ATG9 complex
|
Atg9a
|
atg9a-/-
|
Neonatal lethal during perinatal starvation
|
191
|
Atg9b
|
|
Currently no KO mouse
|
ATG12 conjugation and LC3 lipidation
|
Atg3
|
atg3-/-
|
Neonatal lethal at P1; many cells contain small ATG16L1-positive structures and scattered phagophores
|
192
|
Atg4a
|
|
Currently no KO mouse
|
Atg4b
|
atg4b-/-
|
Viable; inner ear developmental defects and associated defects in balance/coordination
|
194
|
Atg4c
|
atg4c-/-
|
Viable; no overt phenotype/fertility defects; decreased starvation-induced autophagy in diaphragm
|
194
|
Atg4d
|
|
Currently no KO mouse
|
|
Atg16l1
|
atg16l1-/-
|
Neonatal lethal during perinatal starvation; induced expression of IL1B
|
195
|
Atg5
|
atg5-/-
|
Neonatal lethal during perinatal starvation
|
199
|
Nes-Cre; Atg5fl/fl
|
Viable; neurological defects appear after 3 weeks of age: growth retardation, ataxia, poor motor coordination, failed clasping response; increased accumulations of ubiquinated proteins; abundant neurodegeneration of cerebellar Purkinje cells
|
202
|
Pcp-Cre; Atg5fl/fl
|
Viable; neurological defects appear after 10 months of age
|
203
|
Atg7
|
atg7-/-
|
Neonatal lethal during perinatal starvation
|
199
|
Nes-Cre; Atg7fl/fl
|
Lethal by 28 weeks of age; abundant neurodegeneration /neuron death in cerebrum and cerebellum, ubiquitinated protein accumulations in remaining neurons; motor and clasping defects
|
205
|
Slc6a3-Cre; Atg7fl/fl
|
Viable; 40% reduction of dopaminergic neurons and 55% reduction in dopamine; ubiquitinated protein accumulations in remaining neurons
|
207
|
En1-Cre; Atg7fl/fl
|
Viable; 60% reduction of dopaminergic neurons and 65% reduction in dopamine; ubiquitinated protein accumulations in remaining neurons; taxic gait
|
207
|
Thtm1(cre)Te-Cre; Atg7fl/fl
|
Viable; 40% reduction of dopaminergic neurons; accumulation of SNCA protein
|
208
|
Camkk2-Cre;Atg7fl/fl
|
Viable; spontaneous tremors in 75% of mice by 6-7 weeks of age
|
210
|
Alb-Cre; Atg7fl/fl
|
Viable; enlarged hepatocytes; hepatomegaly; accumulation of peroxisomes and mitochondria
|
211
|
Rip-Cre; Atg7fl/fl
|
Viable; hypoinsulinemia and hyperglycemia; reduced number of insulin granules; swelling of mitochondria, rough ER, Golgi
|
212
|
Lc3b
|
lc3b-/-
|
Viable; no overt phenotype/fertility defects
|
214
|
Gabarap
|
gabarap-/-
|
Viable; no overt phenotype/fertility defects
|
215
|
Autophagy-modifying models
|
Sqstm1
|
sqstm1-/-
|
Alzheimer-like phenotype; accumulation of ubiquitinated proteins in neurons and various tissues
|
221
|
Park2
|
park2-/-
|
40% increase in fatalities from induced myocardial infarction due to mitophagy defect
|
224
|
| Mfn2 |
mfn2-/- (cardiac specific) |
Increased sensitivity to ischemia and late onset cardiac dysfunction |
228 |
