Phenotypes Associated with This Genotype

Genotype
MGI:5512702

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA)0Olri/0
• Genetic Background: involves: C57BL/6

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

behavior/neurological

abnormal motor learning ( J:132774 )

• in the accelerated rotarod, mutants do not show short-term improvement between trial 1 and trial 2 as in controls, indicating impaired motor skill learning

abnormal long-term spatial reference memory ( J:132774 )

• 52 week old mutants show impaired memory retention in the Morris water maze when tested 7 days later for their platform preference

abnormal motor coordination/balance ( J:132774 )

• progressive impairment of motor performance that begins around 30 weeks of age

impaired coordination ( J:132774 )

• mice show impaired performance on the rotarod as early as 18 weeks of age, however progressive decline does not start before 30 weeks of age

• progressive motor decline is not reversed by treatment with doxycycline but it does halt further decline

nervous system

abnormal neuron differentiation ( J:132774 )

• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis

• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis

abnormal substantia nigra morphology ( J:132774 )

• dark cells in the substantia nigra and axonal pathology with condensed mitochondria and lipid droplets indicating degeneration of nigral cells

abnormal substantia nigra pars reticulata morphology ( J:132774 )

• large lipid-like drops are seen between nerve fibers of the pars reticulata

hippocampus pyramidal cell degeneration ( J:132774 )

• dark degenerated pyramidal cells are scattered between unaffected neurons

decreased dopaminergic neuron number ( J:132774 )

• reduction of dopaminergic neurons in the substantia nigra; degenerating cells are most prominent in the pars reticulata

abnormal synaptic bouton morphology ( J:132774 )

• reduction of dopamine trasnporter binding sites at presynaptic terminals

decreased neuronal precursor cell number ( J:132774 )

• total number of neuroblasts is reduced in the hippocampus

neuron degeneration ( J:132774 )

• degenerated neurons are seen in the hippocampus and substantia nigra, with darkened nuclear and cytoplasmic appearance, slightly collapsed nuclear envelope, and increased accumulation of lysosomes

hippocampal neuron degeneration ( J:132774 )

• proximal dendrites of the CA3 neurons show signs of degeneration

• dark cell degeneration in the CA1 pyramidal cells as well as in interneurons and granule cells of the dentate gyrus

alpha-synuclein inclusion body ( J:132774 )

• many alpha-synuclein positive mossy fiber terminals, which may show swollen vesicles and enlarged mitochondria, form asymmetric contracts with immunonegative dendritic spines

• alpha-synuclein accumulates in the stratum lacunosum moleculare and in mossy fibers and their terminals

cellular

abnormal neuron differentiation ( J:132774 )

• mice show a 49% reduction of newly differentiated neurons in the granular cell layer of the dentate gyrus, and a reduction of DCX-positive neuroblasts, indicating impaired neurogenesis

• doxycycline treatment to inhibit transgene expression starting at 16 weeks of age does not result in reduced neurogenesis

homeostasis/metabolism

decreased dopamine level ( J:132774 )

• reduction of dopamine level in the olfactory bulb in aged mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:132774