Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-LRRK2*G2019S)E3Cai
• Allele Name: transgene insertion E3, Huaibin Cai
• Allele ID: MGI:4420755
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)885Dbo/0 Tg(tetO-LRRK2*G2019S)E3Cai/0	involves: C3H/HeJ * C57BL/6	MGI:4421004
cx2	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0	involves: C57BL/6	MGI:4420999
cx3	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0 Tg(tetO-SNCA*A53T)E2Cai/0	involves: C57BL/6	MGI:4421000
cx4	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0 Tg(tetO-SNCA)1Cai/0	involves: C57BL/6	MGI:4421005

Genotype
MGI:4421004

cx1

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)885Dbo/0; Tg(tetO-LRRK2*G2019S)E3Cai/0
• Genetic Background: involves: C3H/HeJ * C57BL/6

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

nervous system

neurodegeneration ( J:156512 )

• no acceleration of degeneration is observed compared to Tg(Camk2a-tTA)1Mmay/Tg(tetO-LRRK2*G2019S)E3Cai mice (G2019S)

Genotype
MGI:4420999

cx2

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0
• Genetic Background: involves: C57BL/6

growth/size/body

decreased body weight ( J:156512 )

• starting at 1 year, mice appear to gain less body weight than non-transgenic and Tg(tetO-LRRK2*G2019S)E3Cai single mutant mice, but are not different from Tg(Camk2a-tTA)1Mmay animals

behavior/neurological

behavior/neurological phenotype ( J:156512 )

N • mice show normal performance in the rotarod test

hyperactivity ( J:156512 )

• mice show significantly increased ambulatory activities starting at 12 months of age; at 12 months mice show a trend to increased rearing activities but this does not reach statistical significance

nervous system

nervous system phenotype ( J:156512 )

N • no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice

N • no increase in reactive astrocytosis or microglial activation are detected in the striatum or cortex at 20 months

N • no alpha-synuclein accumulation is observed in neurons at 20 months

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented

• at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons

• at 1 month, the medial/trans-Golgi in neurons is significantly altered

abnormal nervous system physiology ( J:156512 )

• brain homogenates moderately elevated levels of ubiquitinated proteins at 18 months compared to non-transgenic controls

Genotype
MGI:4421000

cx3

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• substantial accumulation of alpha-synuclein is detected in cell bodies at 1 month

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

abnormal dorsal striatum morphology ( J:156512 )

astrocytosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of GFAP-positive cells are higher than in A53T/LRRK2WT mice

abnormal neuron morphology ( J:156512 )

• the Golgi complex is drastically altered in neurons at 1 month with severely fragmented

• at 1 month, the medial/trans-Golgi in neurons is severely fragmented

abnormal neuron mitochondrial morphology ( J:156512 )

• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional

alpha-synuclein inclusion body ( J:156512 )

• a significant increase in detergent-insoluble high molecular weight (HMW) alpha synuclein is detected in 1 month old mice compared to A53T age-matched mice

neurodegeneration ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• dramatic loss (>85%) of striatal neurons is seen in the dorsal striatum

hematopoietic system

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

immune system

microgliosis ( J:156512 )

• exacerbated in the striatum compared to A53T mice at 1 month of age

• levels of microglial activation are higher than in A53T/LRRK2WT mice

cellular

abnormal neuron mitochondrial morphology ( J:156512 )

• in striatal neurons at 1 month, numerous mitochondria have denser matrices and widened cristae compared to controls or A53T mice (seen with 3.5x greater frequency than in A53T mice); these mitochondria are not functional

Genotype
MGI:4421005

cx4

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-LRRK2*G2019S)E3Cai/0; Tg(tetO-SNCA)1Cai/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal nervous system morphology ( J:156512 )

• somatic alpha synuclein in neurons is apparent at 1 month