Phenotypes Associated with This Genotype

Genotype
MGI:5824119

• Allelic Composition: Tsc2^tm1Djk/Tsc2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

behavior/neurological

abnormal response to novel object ( J:217829 )

♂ • male adolescent mice spend less time exploring the novel object than wild-type mice in the novel object recognition test

♂ • however, male adolescent mice do not exhibit repetitive behaviors, motor defects or anxiety-like behaviors in the open field

abnormal social investigation ( J:217829 )

♂ • in the three-chamber social test, male adolescent mice show a preference for interacting with a social target compared with nonsocial target, and the preference index (the ratio of time sniffing mouse versus nonsocial target) is decreased

♂ • treatment with rapamycin rescues social deficits (normalizes sociability and social novelty preferences

abnormal response to social novelty ( J:217829 )

♂ • male adolescent (P30-P35) mice spend less time sniffing the stimulus mouse during a dyadic social interaction with a novel mouse, indicating impaired social interactions

♂ • in the social novelty test, adolescent males spend a similar amount of time sniffing both novel and familiar targets, with decreased preference index (the ratio of time sniffing a stranger mouse versus a familiar mouse), indicating a reduced preference for social novelty

cellular

abnormal autophagy ( J:217829 )

♂ • basal autophagy is suppressed in the brain

♂ • rapamycin treatment normalizes autophagy

♂ • accumulation of lipid droplets and damaged mitochondria in primary neuronal cultures, indicating impaired autophagy

nervous system

abnormal dendritic spine morphology ( J:217829 )

♂ • density of dendritic spines in pyramidal neuron basal dendrites of layer V A1/S2 in temporal cortex is increased in adolescent males

♂ • similar numbers of spines are seen at P19-P20 as in wild-type mice but far more spines in P29-P30 mutants, indicating a lack of normal spine pruning, with only 26% of spines being pruned

♂ • mice treated with an intraperitoneal injection of rapamycin show a correction of the pruning defect

homeostasis/metabolism

abnormal autophagy ( J:217829 )

♂ • basal autophagy is suppressed in the brain

♂ • rapamycin treatment normalizes autophagy

♂ • accumulation of lipid droplets and damaged mitochondria in primary neuronal cultures, indicating impaired autophagy

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:217829