Phenotypes Associated with This Genotype

Genotype
MGI:6852560

• Allelic Composition: Tg(DBH-SNCA)#Dwei/0
• Genetic Background: C57BL/6N-Tg(DBH-SNCA)#Dwei

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

behavior/neurological

impaired contextual conditioning behavior ( J:296218 )

• mice exhibit increased freezing behavior during the fear-training session and during the contextual test at 14 months of age, but not at 3 months or 24 months of age

• however, no differences in freezing behavior are seen in the cued test

increased anxiety-related response ( J:296218 )

• mice show an increase in the number of marbles buried in the marble-burying assay at 14 and 24 months of age, but not at 3 months of age

increased thigmotaxis ( J:296218 )

• in the open field test, mice show an increase in the latency to re-enter the center of the testing field at 14 months of age, but not at 3 or 24 months of age, indicating increased anxiety-like phenotype

• however, mice show normal locomotion over 24 hours at 3, 14, and 24 months of age

increased fear-related response ( J:296218 )

• mice exhibit increased freezing behavior during the fear-training session and during the contextual test at 14 months of age, but not at 3 months or 24 months of age

increased freezing behavior ( J:296218 )

• mice exhibit increased freezing behavior during the fear-training session and during the contextual test at 14 months of age, but not at 3 months or 24 months of age

• however, no differences in freezing behavior are seen in the cued test

abnormal sleep behavior ( J:296218 )

• mice exhibit an increase in sleep latency (take longer to fall asleep) at 3 and 14 months of age, but not at 24 months, indicating an elevated arousal

• treatment with a cocktail of propranolol (beta-adrenergic receptor antagonist) and prazosin (alpha1-adrenergic receptor antagonist) normalizes sleep latency in 3- and 14-month-old mice

homeostasis/metabolism

abnormal nervous system dopamine level ( J:296218 )

• the ratio of the dopamine metabolite DOPAC to dopamine in the striatum, but not the hippocampus, is reduced at 24 months of age, indicating decreased dopamine turnover

• however, norepinephrine and dopamine are not affected in the hippocampus or striatum at any age

nervous system

abnormal locus ceruleus morphology ( J:296218 )

• locus ceruleus neurons show alpha-synuclein oligomeric aggregates in 14- and 24-month-old mice, however mature higher-order alpha-synuclein inclusions are not seen

• mice exhibit elevation of tyrosine hydroxylase in the locus ceruleus at 3 and 14 months of age

• mice show a reduction in locus ceruleus fibers in the dentate gyrus at 24 months of age, with a trend for reduction in CA1 and CA3 of the hippocampus, indicating degeneration of hippocampal locus ceruleus fibers

• mice exhibit a decrease in the number of Iba1-expressing cells in the locus ceruleus at 14 months of age, but not 3 or 24 months of age

abnormal hippocampus CA1 region morphology ( J:296218 )

• mice exhibit a decrease in the number of Iba1-expressing cells in in the CA1 region of the hippocampus at 14 months of age, but not 3 or 24 months of age

astrocytosis ( J:296218 )

• astrogliosis is seen in the locus ceruleus at 24 months of age, but not at 3 or 14 months of age

• hippocampal astrogliosis is seen in the CA1 and CA at 14 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:296218