Phenotypes Associated with This Genotype

Genotype
MGI:5289971

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-SNCA*A53T)33Vle/0
• Genetic Background: involves: C3H/HeH * C57BL/6

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

nervous system

increased neuron apoptosis ( J:156801 )

• dentate gyrus neuron loss is due to cell death not decreased cell proliferation

abnormal dentate gyrus morphology ( J:156801 , J:174555 )

• mild hippocampal dentate gyrus neuron atrophy is seen at P14, and is striking by P21 (J:156801)

• mice treated with doxycycline to suppress alpha-synuclein expression, do not exhibit neuron atrophy (J:156801)

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of dentate gyrus granule cells (J:174555)

decreased hippocampus pyramidal cell number ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe loss of hippocampal pyramidal cells

thin cerebral cortex ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit severe reduction in cortex thickness

gliosis ( J:156801 )

• gliosis in the hippocampus, near the dentate gyrus

astrocytosis ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit progressive reactive astrogliosis; mutants further treated with doxycycline at 9 months, show prevention of further reactive gliosis

abnormal synaptic bouton morphology ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit a reduction in presynaptic vesicle proteins indicating a disruption in synaptic vesicles in the mossy fiber terminals

alpha-synuclein inclusion body ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit abnormal accumulation of alpha-synuclein in limbic areas including the cingulated cortex, the hippocampus, dentate gyrus, and mammillary body, as well as the olfactory bulb, septum and subthalamic nucleus, by 4 months of age; superior colliculus, ventral tegmental area, brainstem, and spinal cord also shows a limited amount of alpha-synuclein accumulation

• young mice (4-12 months) fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce expression exhibit early, soluble, neuritic, and synaptic accumulations, which over time progress to become insoluble cytoplasmic inclusions at 20 months

• mice treated with doxycyline starting at 9 months for 3 months and analyzed at 12 months do not exhibit abnormal alpha-synuclein accumulations in the hippocampus or dentate gyrus; doxycycline however did not clear alpha-synuclein pathology in the mammillary bodies, olfactory bulb or septum, but did arrest further accumulation progression

neurodegeneration ( J:174555 )

• neuronal loss in the cortex and hippocampus is seen in 20-22 old mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression

hippocampal neuron degeneration ( J:156801 )

• postmitotic hippocampal dentate gyrus neuron degeneration is seen by P14, but no degeneration of proliferating cells

behavior/neurological

impaired contextual conditioning behavior ( J:174555 )

• mutants fed a doxycycline diet to suppress transgene expression from E0.5 until P21 and then switched to a regular diet to induce transgene expression exhibit impaired contextual fear memory at 8 months of age; mutants further treated with doxycycline at 9 months show improved memory function

• normal chow-fed mutants at 12 months of age show impaired contextual fear memory

cellular

increased neuron apoptosis ( J:156801 )

• dentate gyrus neuron loss is due to cell death not decreased cell proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lewy body dementia		DOID:12217	OMIM:127750	J:174555