Phenotypes Associated with This Genotype

Genotype
MGI:4417912

• Allelic Composition: Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte/Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte
• Genetic Background: involves: C57BL/6 * CBA

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

Amyloid pathology and glial inflammation in hemizygous and homozygous Tg(Thy1-PSEN1*M146V,-APP*Swe)10Arte mouse brain

mortality/aging

decreased survivor rate ( J:155410 )

• mice exhibit 85% survival

premature death ( J:155410 )

• 2 of 13 mice die before 12 months of age

nervous system

microgliosis ( J:155410 )

amyloid beta deposits ( J:155410 )

• as early as 3 to 5 months, mice exhibit plaques in the anterior neocortex and subiculum unlike wild-type mice

• mmice exhibit plaque accumulation in the posterior neocortex, CA1 through 4 regions of the hippocampus, amygdala and related limbic structures, and thalamus unlike in wild-type mice

• plaques also accumulate in the olfactory bulb, colliculi, brainstem, and the striatum

• at 8 months, large plaques develop in the thalamus compared with wild-type mice

• older mice develop diffuse deposits of beta-amyloid

• plaque size increases with age

cerebral amyloid angiopathy ( J:155410 )

astrocytosis ( J:155410 )

abnormal neurite morphology ( J:155410 )

• dense-core plaques are encompassed by a sphere of early-dystrophic, swollen neurites with ubiquitin accumulation unlike in wild-type mice

behavior/neurological

abnormal object recognition memory ( J:155410 )

• at 12 months, mice exhibit a deficit in episodic memory with reduced exploration of a novel object compared with wild-type mice

abnormal spatial learning ( J:155410 )

• at 12 months, mice exhibit reduced performance in a Morris water maze test compared with wild-type mice

abnormal spatial working memory ( J:155410 )

• at 12 months, mice from the cross-sectional cohort display poor memory in a Morris water maze compared with wild-type mice

increased anxiety-related response ( J:155410 )

• at 4 months but not in older mice, anxiety related behaviors are increased with mice spending less time in the center of an open field and entering the open sector of a zero maze compared with wild-type mice

abnormal response to novel object ( J:155410 )

• at 12 months, mice exhibit a deficit in episodic memory with reduced exploration of a novel object compared with wild-type mice

decreased locomotor activity ( J:155410 )

• at 4 months but not in older mice, exploratory activity is decreased in a Y maze compared with wild-type mice

immune system

microgliosis ( J:155410 )

hematopoietic system

microgliosis ( J:155410 )

homeostasis/metabolism

amyloidosis ( J:155410 )

amyloid beta deposits ( J:155410 )

• as early as 3 to 5 months, mice exhibit plaques in the anterior neocortex and subiculum unlike wild-type mice

• mmice exhibit plaque accumulation in the posterior neocortex, CA1 through 4 regions of the hippocampus, amygdala and related limbic structures, and thalamus unlike in wild-type mice

• plaques also accumulate in the olfactory bulb, colliculi, brainstem, and the striatum

• at 8 months, large plaques develop in the thalamus compared with wild-type mice

• older mice develop diffuse deposits of beta-amyloid

• plaque size increases with age

cerebral amyloid angiopathy ( J:155410 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:155410