Phenotypes Associated with This Genotype

Genotype
MGI:5641483

• Allelic Composition: Tsc1^tm1Djk/Tsc1^tm1Djk; Tg(Pcp2-cre)2Mpin/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/cJ * C57BL/6J

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

behavior/neurological

abnormal learning/memory/conditioning ( J:186699 )

♂ • mice exhibit similar acquisition learning of a submerged escape-platform location compared to controls, however when the escape platform location is reversed, mutants show impaired learning of the new platform location

♂ • rapamycin treatment prevents the reversal learning impairment

abnormal response to novel odor ( J:186699 )

♂ • mice show reduced investigation of social odors compared with controls, suggesting impaired discrimination of social olfactory cues

♂ • however, mice show normal investigation of non-social olfactory cues

increased grooming behavior ( J:186699 )

♂ • increase in self-grooming rates

ataxia ( J:186699 )

♂ • mutants show initial signs of ataxia at 7-8 weeks of age which progresses with age

♂ • mice show decreased stride length and increased stride width at 4 months of age

♂ • rapamycin treated mutants do not show ataxic gait

impaired coordination ( J:186699 )

♂ • mutants show impaired motor learning on the accelerating rotarod test before ataxia onset

♂ • treatment with rapamycin prevents the motor phenotypes

short stride length ( J:186699 )

♂

abnormal sexual interaction ( J:186699 )

♂ • mice show impaired male-female social interactions, with reductions in the time that mice spend interacting compared to controls

abnormal social investigation ( J:186699 )

♂ • in a 3-chambered assay of social approach and preference for social novelty, mice show social impairments, showing no differences between the time spend in the chamber or in interaction with the novel mouse versus the novel object

♂ • in a social novelty paradigm, mice show no preference for social novelty

♂ • treatment with rapamycin results in normal social behavior

excessive vocalization ( J:186699 )

• P5-P12 pups show increased vocalizations

nervous system

abnormal cerebellar Purkinje cell layer ( J:186699 )

• cerebellar Purkinje cell layer is abnormal with increased soma area and reduced Purkinje cell numbers

• treatment with rapamycin starting at P7 prevents the Purkinje cell defects

abnormal Purkinje cell morphology ( J:186699 )

• Purkinje cell soma area is increased at 4 weeks of age

• markers for endoplasmic reticulum and oxidative stress are elevated indicating elevated neuronal stress of Purkinje cells

abnormal Purkinje cell axon morphology ( J:186699 )

• Purkinje cells display abnormal axonal projections with numerous protrusions and abnormal collateralization

abnormal Purkinje cell dendrite morphology ( J:186699 )

• increase in spine density on Purkinje cell dendrites

decreased Purkinje cell number ( J:186699 )

• decrease in Purkinje cell numbers are first seen at 2 months of age, with a further reduction at 4 months

• an increase in Purkinje cell apoptosis is seen at 7-8 weeks of age

abnormal nervous system physiology ( J:186699 )

• Purkinje cell excitability is reduced, with Purkinje cells showing lower, graded spontaneous spiking rate, and current injection evokes fewer action potentials in Purkinje cells

• injection of small hyperpolarizing currents results in smaller voltage changes in Purkinje cells, indicating a decrease in the effective input resistance

• despite receiving normal functioning synaptic inputs, the output of the cerebellar cortex is reduced, both tonically and in response to incoming excitatory drive

• however, alterations in synaptic transmission are not apparent in mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:186699