Phenotypes associated with this allele

• Allele Symbol: Lrrk2⁺
• Allele Name: wild type
• Allele ID: MGI:3055129
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Lrrk2^tm4.1Arte/Lrrk2^+	C57BL/6-Lrrk2^tm4.1Arte/Tac	MGI:6798089
ht2	Lrrk2^tm1.1Dlbe/Lrrk2^+	C57BL/6NTac-Lrrk2^tm1.1Dlbe	MGI:6273312
ht3	Lrrk2^tm1.1Hlme/Lrrk2^+	involves: C57BL/6 * C57BL/6J	MGI:5750897
cx4	Lrrk2^tm1.1Cai/Lrrk2^+ Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: 129X1/SvJ * C57BL/6	MGI:4421006

Genotype
MGI:6798089

ht1

• Allelic Composition: Lrrk2^tm4.1Arte/Lrrk2⁺
• Genetic Background: C57BL/6-Lrrk2^tm4.1Arte/Tac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

abnormal brain interneuron morphology ( J:312767 )

• loss of primary cilia on choline acetyltransferase interneurons of the dorsal striatum that is less severe than in Tg(LRRK2*G2019S)2AMjff mice

• fewer and shorter cilia on striatal astrocytes

• treatment with an LRRK2 inhibitor (MLi- 2) fails to restore cilia

• however, cilia on primarily medium spiny neurons are normal

abnormal dorsal striatum morphology ( J:312767 )

• loss of primary cilia on choline acetyltransferase interneurons of the dorsal striatum that is less severe than in Tg(LRRK2*G2019S)2AMjff mice

• fewer and shorter cilia on striatal astrocytes

• treatment with an LRRK2 inhibitor (MLi- 2) fails to restore cilia

• however, cilia on primarily medium spiny neurons are normal

Genotype
MGI:6273312

ht2

• Allelic Composition: Lrrk2^tm1.1Dlbe/Lrrk2⁺
• Genetic Background: C57BL/6NTac-Lrrk2^tm1.1Dlbe

nervous system

increased excitatory postsynaptic current frequency ( J:234639 )

• dorsal striatal spiny projection neurons exhibit increased frequency of sEPSCs

• however, by P60, sEPSC frequencies are similar to wild-type

Genotype
MGI:5750897

ht3

• Allelic Composition: Lrrk2^tm1.1Hlme/Lrrk2⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J

behavior/neurological

abnormal motor coordination/balance ( J:223350 )

• mice exhibit a slightly better performance on motor testing at 6 months of age but no differences were seen at 12 months

cellular

abnormal mitochondrial morphology ( J:223350 )

• mitochondria in the striatum of 15 month old mice have altered distribution, clustering in the neuropils, and a few have altered shape and crista morphology

abnormal mitochondrial crista morphology ( J:223350 )

• a few mitochondria in the striatum of 15 month old mice have altered crista morphology

abnormal mitochondrial shape ( J:223350 )

• a few mitochondria in the striatum of 15 month old mice have altered shape

homeostasis/metabolism

abnormal dopamine level ( J:223350 )

• the average DOPAC/dopamine and homovanillic acid /dopamine ratios at baseline are almost double compared to wild-type ratios

• however, the average level of extracellular metabolites homovanillic acid and DOPAC remains similar to wild-type mice

nervous system

tau protein deposits ( J:223350 )

• the corpus callosum shows heavier tau staining and slightly increased cortical tau

• tau immunoreactivity is increased in some nuclear groups, particularly the thalamic parafasicular nuclei, the sub-thalalmic nucleus, pre-mammillary nuclei and the lateral hypothalamus

abnormal synaptic dopamine release ( J:223350 )

• basal dopamine and amphetamine-stimulated extracellular release of dopamine is decreased in the striatum at 12, but not 6, months of age

Genotype
MGI:4421006

cx4

• Allelic Composition: Lrrk2^tm1.1Cai/Lrrk2⁺; Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• somatic alpha synuclein in neurons is apparent at 12 months

astrocytosis ( J:156512 )

• significant at 12 months

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

abnormal striatum morphology ( J:156512 )

• numbers of residual neurons is significantly lower than non transgenic controls

abnormal neuron morphology ( J:156512 )

• the Golgi complex shows severe fragmentation in 12 month old animals

neurodegeneration ( J:156512 )

• neurodegeneration significant at 12 months

immune system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

hematopoietic system

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months

cellular

astrocytosis ( J:156512 )

• significant at 12 months

microgliosis ( J:156512 )

• increased microglial activation is observed in the brain at 12 months