Phenotypes associated with this allele

• Allele Symbol: Slc6a3^tm4.1(tTA)Xz
• Allele Name: targeted mutation 4.1, Xiaoxi Zhuang
• Allele ID: MGI:5619093
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Pink1^tm1Zhzh/Pink1^tm1Zhzh Slc6a3^tm4.1(tTA)Xz/? Tg(tetO-SNCA*A53T)E2Cai/?	involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6	MGI:5619815
cx2	Slc6a3^tm4.1(tTA)Xz/Slc6a3^+ Tg(tetO-SNCA*A53T)E2Cai/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6	MGI:5619812
cx3	Prkn^tm1Shn/Prkn^tm1Shn Slc6a3^tm4.1(tTA)Xz/? Tg(tetO-SNCA*A53T)E2Cai/?	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6	MGI:5619814

Genotype
MGI:5619815

cx1

• Allelic Composition: Pink1^tm1Zhzh/Pink1^tm1Zhzh; Slc6a3^tm4.1(tTA)Xz/?; Tg(tetO-SNCA*A53T)E2Cai/?
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

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

cellular

abnormal mitochondrial morphology ( J:218892 )

• 51% reduction of mitochondrial mass at 3 weeks of age

nervous system

neuronal cytoplasmic inclusions ( J:218892 )

• "mitochondrial inclusions are observed in in dopaminergic neurons beginning at 3 weeks of age

• inclusions average 4.2 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)

• number of inclusions is approximately 1.4 inclusions per dopaminergic neuron

Genotype
MGI:5619812

cx2

• Allelic Composition: Slc6a3^tm4.1(tTA)Xz/Slc6a3⁺; Tg(tetO-SNCA*A53T)E2Cai/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

nervous system

loss of dopaminergic neurons ( J:218892 )

• 21% dopaminergic neuron loss in the substantia nigra pars compacta (SNc) by 3 months of age

• 35% loss by 6 months of age

• loss appears to stop or slow between 6 and 12 months

• dopamine turnover rate is increased by 29%

• decrease in TH (tyrosine hydroxylase) terminal staining in the dorsal, but not ventral, striatum of 12 month old mice

abnormal axon morphology ( J:218892 )

• 25 fold increase in enlarged axon varicosities in midbrain region at 6 weeks of age

• varicosities are approximately 10 um in diameter, are oval-shaped and have a hollowed core

abnormal dendrite morphology ( J:218892 )

• fragmented dendrites are observed in the substantia nigra pars reticulata at 6 weeks of age

neuron degeneration ( J:218892 )

neuronal cytoplasmic inclusions ( J:218892 )

• "mitochondrial inclusions" are observed in dopaminergic neurons beginning at 3 weeks of age

• inclusions are 0.5-2 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)

• number of inclusions is approximately 1.6 inclusions per dopaminergic neuron at 3 weeks of age

• inclusions are distributed in soma and proximal processes of dopaminergic neurons

• inclusions are mostly restricted to substantia nigra pars compacta

• the number of inclusions is decreased by 6 months of age

growth/size/body

slow postnatal weight gain ( J:218892 )

homeostasis/metabolism

decreased dopamine level ( J:218892 )

• levels of dopamine and its metabolites (DOPA and HVA) are decreased by 54% in 7-11 month old mice in striatal tissue

cellular

abnormal mitochondrial shape ( J:218892 )

• mitochondria in dopaminergic neurons appears fragmented by 6 weeks of age

decreased mitochondrial size ( J:218892 )

• mitochondrial length is decreased by 61% in mitochondria from dopaminergic neurons, however, mitochondrial mass is similar to controls

abnormal mitochondrial physiology ( J:218892 )

• multiple senescent mitochondria are observed in dopaminergic neurons as compared to controls

• senescent mitochondria exhibit disordered cristae, swollen matrix and the absent outer membranes

Genotype
MGI:5619814

cx3

• Allelic Composition: Prkn^tm1Shn/Prkn^tm1Shn; Slc6a3^tm4.1(tTA)Xz/?; Tg(tetO-SNCA*A53T)E2Cai/?
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

nervous system

neuronal cytoplasmic inclusions ( J:218892 )

• "mitochondrial inclusions are observed in in dopaminergic neurons beginning at 3 weeks of age

• inclusions average 4.4 um in diameter and are labeled by mitochondrial markers (COX1, SOD2)

• number of inclusions is approximately 1.7 inclusions per dopaminergic neuron

cellular

abnormal mitochondrial morphology ( J:218892 )

• 57% reduction of mitochondrial mass at 3 weeks of age