Phenotypes Associated with This Genotype

Genotype
MGI:6113542

• Allelic Composition: Rrn3^tm1.1Igt/Rrn3^tm1.1Igt; Tg(Slc6a3-cre/ERT2)1Span/0
• Genetic Background: involves: 129/Sv * C57BL/6

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:168232 )

• motor dysfunction in mice injected with tamoxifen at 2 months of age

cellular

abnormal nucleolus morphology ( J:242309 )

• nucleolar integrity is disrupted in dopaminergic neurons of tamoxifen treated mice

abnormal mitochondrial morphology ( J:168232 )

• about 40% decrease in COX activity is seen 2 weeks after tamoxifen treatment, indicating mitochondrial damage is an early consequence of nucleolar damage

abnormal cell physiology ( J:242309 )

• induction of nucleolar stress is seen in dopaminergic neurons of tamoxifen treated mice

increased cellular sensitivity to oxidative stress ( J:168232 )

• dopaminergic neurons of tamoxifen-induced mice are more vulnerable to the oxidative damage induced by MPTP than controls showing an approximate 40% loss of neurons compared to 15% in controls

oxidative stress ( J:168232 )

• dopaminergic neurons show higher levels of oxidative stress markers at 4 weeks after tamoxifen treatment

homeostasis/metabolism

decreased dopamine level ( J:168232 )

• mice injected with tamoxifen at 2 months of age exhibit a decline in dopamine content in the striatum

nervous system

loss of dopaminergic neurons ( J:168232 )

• mice injected with tamoxifen at 2 months of age show a progressive differential loss of dopaminergic neurons in substantia nigra and ventral tegmental area

• tamoxifen-induced mice treated with pifithrin-alpha, a chemical inhibitor of Trp53 show prevention of dopaminergic neuron loss

neurodegeneration ( J:168232 )

• mice injected with tamoxifen at 2 months of age exhibit neurodegeneration of TH+ neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:168232 , J:242309