Phenotypes Associated with This Genotype

Genotype
MGI:5604280

• Allelic Composition: En1^tm2Alj/En1⁺; Tg(Th-EGFP)6-7Okn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J * OF1

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

nervous system

decreased dopaminergic neuron number ( J:214073 )

• nigral tyrosine hydroxylase-positive dopaminergic (TH) neurons are reduced in number by 18% as compared to controls beginning at 16 weeks of age, progressing to 40% at 24 weeks

• numbers of TH+ neurons are similar to controls at 4 weeks

neurodegeneration ( J:214073 )

axon degeneration ( J:214073 )

• progressive degeneration of nigrostriatal axon terminals

axonal dystrophy ( J:214073 )

• enlarged axon terminals contain accumulations of abnormal mitochondria, electron-dense bodies, and abnormal autophagolysosomes

• enlarged axons from the median forebrain bundle appear fragmented and swollen

axonal spheroids ( J:214073 )

• nigrostriatal neurons exhibit spheroidal dystrophic axon terminals beginning at 8 days

• spheroids contain electron dense autophagic vacuoles

abnormal synaptic dopamine release ( J:214073 )

• nigrostriatal terminals in the dorsal striatum of 16 week old mice are deficient in KCl-evoked dopamine release and uptake

homeostasis/metabolism

abnormal autophagy ( J:214073 )

• autophagic protein degradation is reduced in dopaminergic neurons

decreased dopamine level ( J:214073 )

• dopamine levels in the striatum of 4 week old mice are 27% lower than controls and progress to 46% by 24 weeks of age

cellular

abnormal autophagy ( J:214073 )

• autophagic protein degradation is reduced in dopaminergic neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:214073