. 2021 Apr 28;22(9):4643. doi: 10.3390/ijms22094643

Table 4.

Findings in animal models related to Prkn, Lrrk2 and Pink1.

Gene	Animal Model (s)	In Vivo	In Vitro	Expression Level	Main Findings	Ref.
PRKN	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Independent regulation of parkin ubiquitination and alpha-synuclein clearance	[96]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Accelerated microtubule aging in dopaminergic neurons	[97]
	B6.129S4-Prkn^tm1Shn/J		X	Prkn KO mice	Myotubular atrophy Impaired mitochondrial function and smaller myofiber area	[98]
	B6.129S4-Prkn^tm1Shn/J		X	Prkn KO mice	Parkin mediates the ubiquitination of VPS35 Reduced WASH complexes	[99]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	ER stress and induced inflammation levels	[100]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Behavioral impairments Amplified EtOH-induced dopaminergic neurodegeneration, oxidative stress and apoptosis Dysfunction of mitochondrial autophagy	[101]
	B6.129S4-Prkn^tm1Shn/J		X	Prkn KO mice	Parkin promotes proteasomal degradation of Synaptotagmin IV	[102]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	SNPH Cargo vesicle generation not affected	[103]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Exacerbated mitochondrial dysfunction in neurons	[104]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Increased sensitivity to myocardial infarction Reduced survival after the infarction Reduced mitophagy	[105]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Parkin antagonizes the death potential of FAF1	[106]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Acutely sensitivity to oxidative stress Inability to maintain Mcl-1 levels Death of dopaminergic neurons	[107,108]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Aberrant behavioral response to dopamine replacement therapy in PD	[109]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Resisted weight gain, steatohepatitis, and insulin resistance Abolished hepatic fat uptake	[110]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Reductions in the total catecholamine release Impaired LTP and LTD Normal levels of dopamine receptors and dopamine transporters	[111]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Requiring inflammatory stimulus for nigral DA neuron loss	[112]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Reduced respiratory capacity mitochondria (in striatal cells) Delayed weight gain Lower protection against ROS	[113]
	B6.129S4-Prkn^tm1Shn/J	X	X	Prkn KO mice	Increased extracellular dopamine concentration in the striatum Deficits in behavioral tests	[114]
	Double-mutant “TwinkPark” mice, resulting from crossing B6.129S4-Prkn^tm1Shn/J line with Twinkle^dup/+ line	X	X	Prkn KO (enhanced in the substantia nigra) mice	Decrease of mitochondrial DNA Low mitochondrial function and membrane potential Neurobehavioral deficits	[115]
	Crossing B6.129S4-Prkn^tm1Shn/J line with a Mcl-1 +/− line (n.s.n.)	X	X	Prkn KO + Mcl-1 +/− mice	Dopaminergic neuron loss Motor impairments	[107]
	B6.129S4-Prkn^tm1Shn/J B6.129S4-Pink1^tm1Shn/J	X	X	-Prkn KO mice -Pink1 KO mice	Inflammation rescued by STING-mediated action	[116]
	B6.129S4-Prkn^tm1Shn/J B6.129S4-Pink1^tm1Shn/J	X	X	-Prkn KO mice -Pink1 KO mice	No repression of mitochondrial antigen presentation	[117]
	B6.129S4-Prkn^tm1Shn/J LEH-Pink1^tm1sage		X	-Prkn KO mice -Pink1 KO rats	Mitophagy of damaged mitochondria in axons requires PINK1 and Parkin	[118]
	Crossing B6.129S4-Prkn^tm1Shn/J line and B6.129S4-Pink1^tm1Shn/J line		X	Prkn/Pink1 double KO mice	Higher levels of ATP synthase Denervated neuromuscular junctions	[119]
	B6.129S4-Prkn^tm1Shn/J B6.129S4-Pink1^tm1Shn/J B6.Cg-Park7^tm1Shn/J	X	X	-Prkn KO mice -Pink1 KO mice -Dj-1 KO mice	Aberrant striatal synaptic plasticity in rodent models of autosomal recessive PD	[120]
	Crossing DA_SYN53 double-transgenic (tetO-SNCAA53T) E2Cai/J line + DAT-PF-tTA) mice with B6.129S4-Prkntm1Shn/J line or with Pink1^tm1Zhzh* mutation line (n.s.n.)	X	X	Overexpressing human A53T-SNCA in DA neurons and KO for either Prkn or Pink1	Pervasive mitochondrial macroautophagy defects Dopamine neuron degeneration	[121]
	B6;129-Pink1^tm1Aub/J		X	Pink1 KO mice	Altered spontaneous EPSCs	[122]
	B6;129-Pink1^tm1Aub/J		X	Pink1 KO mice	Mitochondrial recruitment of parkin not affected	[123]
	B6;129-Pink1^tm1Aub/J	X	X	Pink1 KO mice	Progressive mitochondrial dysfunction in absence of neurodegeneration	[124]
LRRK2	B6.129X1(FVB)-Lrrk2^tm1.1Cai/J		X	Lrrk2 KO mice	Alterations in protein synthesis Alterations in degradation pathways	[125]
	B6.129X1(FVB)-Lrrk2^tm1.1Cai/J	X	X	Lrrk2 KO mice	LRRK2 regulates synaptogenesis and dopamine receptor activation	[126]
	B6.129X1(FVB)-Lrrk2^tm1.1Cai/J		X	Lrrk2 KO mice	LRRK2 regulates ER-Golgi export	[127]
	B6.129X1(FVB)-Lrrk2^tm1.1Cai/J	X		Lrrk2 KO mice	Neurons have more motile axonal and dendritic growth	[128]
	C57BL/6-Lrrk2^tm1Mjfa/J	X	X	Lrrk2 KO mice	LRRK2 modulates microglial phenotype and dopaminergic neurodegeneration	[129]
	C57BL/6-Lrrk2^tm1Mjfa/J		X	Lrrk2 KO mice	Stress-Related Gastrointestinal Dysmotility	[130]
	C57BL/6-Lrrk2^tm1Mjfa/J		X	Lrrk2 KO mice	LRRK2 is required for Rip2 localization to DCVs	[131]
	C57BL/6-Lrrk2^tm1Mjfa/J		X	Lrrk2 KO mice	Significant increase of ceramide levels Direct effects on GBA1	[132]
	B6;129-Lrrk2^tm2.1Shn/J	X	X	Lrrk2 KO mice	Impairment of Autophagy	[133]
	B6;129-Lrrk2^tm2.1Shn/J B6;129-Lrrk2^tm3.1Shn/J		X	Lrrk2 KO mice	Impairment of protein degradation pathways Apoptotic cell death	[134]
	C57BL/6-Lrrk2^tm1.1Mjff/J	X	X	Lrrk2 KO mice	No obvious bone alteration phenotypes	[135]
	B6.Cg-Tg(Lrrk2)6Yue/J	X	X	Lrrk2 overexpressing mice	Autophagy suppression	[136]
	B6.FVB-Tg (LRRK2) WT1Mjfa/J	X	X	LRRK2 overexpressing mice	Behavioral hypoactivity Altered dopamine-dependent short-term plasticity	[137]
	STOCK Tg (tetO-LRRK2*G2019S) E3Cai/J		X	G2019S-LRRK2 overexpressing mice	Perturbed homeostasis Altered neuronal morphogenesis	[138]
	B6.Cg-Tg (Lrrk2*G2019S) 2Yue/J		X	G2019S-LRRK2 overexpressing mice	Reduction in lysosomal pH Increased expression of lysosomal ATPases	[139]
	B6.FVB-Tg (LRRK2*G2019S) 1Mjfa/J	X	X	G2019S-LRRK2 overexpressing mice	Synapsis gain-of-function effect of the G2019S mutation	[140]
	NTac:SD-Tg (LRRK2*G2019S) 571CJLi	X	X	G2019S-Lrrk2 overexpressing rats	Altered bone marrow myelopoiesis Peripheral myeloid cell differentiation	[141]
	NTac:SD-Tg (LRRK2*G2019S) 571CJLi	X	X	G2019S-Lrrk2 overexpressing rats	Enhanced α-syn gene-induced neurodegeneration	[142]
	K-14Cre-positive Gba^lnl/lnl		X	Gba KO mice (except in skin)	Reduced cerebral vascularization	[143]
PINK1	B6.129S4-Pink1^tm1Shn/J		X	Pink1 KO mice	Pink1 is not required for ubiquitination of mitochondrial proteins	[144]
	B6.129S4-Pink1^tm1Shn/J	X	X	Pink1 KO mice	Reduced motor activity Slower locomotor activity time Absence of nigrostriatal dopamine loss	[145]
	B6.129S4-Pink1^tm1Shn/J		X	Pink1 KO mice	Impaired mitochondrial trafficking Fragmented mitochondria	[146]
	B6.129S4-Pink1^tm1Shn/J	X	X	Pink1 KO mice	Hypersensitivity to MPTP-induced dopaminergic neuronal loss	[147]
	B6.129S4-Pink1^tm1Shn/J		X	Pink1 KO mice	No significant change in Ca²⁺ currents	[148]
	B6.129S4-Pink1^tm1Shn/J	X	X	Pink1 KO mice	Pathological cardiac hypertrophy Greater levels of oxidative stress Impaired mitochondrial function	[149]
	B6.129S4-Pink1^tm1Shn/J	X	X	Pink1 KO mice	Impairments of corticostriatal LTP and LTD Impaired dopamine release	[150]
	n.s.n.		X	Pink1 KO mice	Intestinal infection triggers Parkinson’s disease-like symptoms	[151]
	Crossing B6;129-Pink1^tm1Aub/J line with dOTC line	X	X	Pink1 KO mice overexpressing OTC in DA neurons	Enhanced neurodegeneration in a model of mitochondrial stress	[152]
	B6.129S4-Pink1^tm1Shn/J B6.129S4-Prkn^tm1Shn/J		X	-Pink1 KO mice -Prkn KO mice	Enhanced sensitivity to group II mGlu receptor activation	[153]
	B6.129S4-Pink1^tm1Shn/J B6.129S4-Prkn^tm1Shn/J		X	-Pink1 KO mice -Prkn KO mice	Reduced mitochondria functions Altered mitophagy in macrophages	[154]
	FVB;129-Pink1^tm1Aub Tg(Prnp-SNCA*A53T)AAub/J		X	A53T-SNCA overexpressing Pink1 KO mice	Altered mitochondrial biogenesis	[155]
	FVB;129-Pink1^tm1Aub Tg(Prnp-SNCA*A53T)AAub/J	X	X	A53T-SNCA overexpressing Pink1 KO mice	Exacerbated synucleinopathy	[156]
	FVB;129-Pink1^tm1Aub Tg(Prnp-SNCA*A53T)AAub/J	X	X	A53T-SNCA overexpressing Pink1 KO mice	Potentiation of neurotoxicity	[157]
	Atad3afl/fl Mx1CrePink1 −/− mice, resulting from crossing B6.129S4-Pink1^tm1Shn/J line with Atad3afl/fl Mx1Cre line	X	X	Pink1 KO + conditional Atad3a KO mice	Aberrant stem-cell and progenitor homeostasis Pink1-dependent mitophagy	[158]
	B6N.129S6(Cg)-Atp13a2^tm1Pjsch/J	X	X	Atp13a2 KO mice	Autophagy impairment Reduced HDAC6 activity	[159]
	B6N.129S6(Cg)-Atp13a2^tm1Pjsch/J		X	Atp13a2 KO mice	Harmful gliosis	[160]
	B6N.129S6(Cg)-Atp13a2^tm1Pjsch/J	X	X	Atp13a2 KO mice	Neuronal ceroid lipofuscinosis Limited α-syn accumulation Sensorimotor deficits	[161]

n.s.n.: Non standard nomenclature.