Phenotypes associated with this allele

• Allele Symbol: Tsc2^tm1Djk
• Allele Name: targeted mutation 1, David J Kwiatkowski
• Allele ID: MGI:1857938
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tsc2^tm1Djk/Tsc2^tm1Djk	either: (involves: 129S4/SvJae * BALB/cJ) or (involves: 129S4/SvJae * Black Swiss) or (involves: 129S4/SvJae * C57BL/6J)	MGI:2174787
ht2	Tsc2^tm1Djk/Tsc2^+	either: (involves: 129S4/SvJae * BALB/cJ) or (involves: 129S4/SvJae * Black Swiss) or (involves: 129S4/SvJae * C57BL/6J)	MGI:2174788
ht3	Tsc2^tm1Djk/Tsc2^+	involves: 129S4/SvJae * C57BL/6J	MGI:5824119
ht4	Tsc2^tm1Djk/Tsc2^+	involves: 129S4/SvJae * C57BL/6NCrl	MGI:3811791
cn5	Tsc2^tm1Djk/Tsc2^+ Atg7^tm1Tchi/Atg7^tm1Tchi Tg(Camk2a-cre)T29-1Stl/0	involves: 129S4/SvJae * BALB/c * C57BL * C57BL/6 * CBA/JNCrlj	MGI:5824126
cx6	Tsc2^tm1Djk/Tsc2^+ Tg(CAG-EGFP/Map1lc3b)53Nmz/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * C57BL/6NCrlj * DBA/2	MGI:5824122

Genotype
MGI:2174787

hm1

• Allelic Composition: Tsc2^tm1Djk/Tsc2^tm1Djk
• Genetic Background: either: (involves: 129S4/SvJae * BALB/cJ) or (involves: 129S4/SvJae * Black Swiss) or (involves: 129S4/SvJae * C57BL/6J)

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

Small size and liver hypoplasia in Tsc2^tm1Djk/Tsc2^tm1Djk embryos

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:57631 )

• age of onset E9.5

liver/biliary system

liver hypoplasia ( J:57631 )

Genotype
MGI:2174788

ht2

• Allelic Composition: Tsc2^tm1Djk/Tsc2⁺
• Genetic Background: either: (involves: 129S4/SvJae * BALB/cJ) or (involves: 129S4/SvJae * Black Swiss) or (involves: 129S4/SvJae * C57BL/6J)

Tsc2^tm1Djk/Tsc2⁺ mice develop renal, liver, lung and extremity tumors

neoplasm

increased tumor incidence ( J:57631 )

• reported at 15 months of age

• Background Sensitivity: note that the tumor expression pattern is influenced by genetic background; authors note fewer large renal cystadenomas in outbred Black Swiss background and more angiosarcomas in 129S4/SvJae chimeric mice

increased hepatic hemangioma incidence ( J:57631 )

• 50% incidence; causes fatal bleeding in 10% of these cases

increased lung adenoma incidence ( J:57631 )

• 32% incidence

increased renal cystadenoma incidence ( J:57631 )

• 100% incidence

increased renal carcinoma incidence ( J:57631 )

• less than 10% incidence

increased extremity angiosarcoma incidence ( J:57631 )

• less than 10% incidence

renal/urinary system

increased renal cystadenoma incidence ( J:57631 )

• 100% incidence

increased renal carcinoma incidence ( J:57631 )

• less than 10% incidence

liver/biliary system

increased hepatic hemangioma incidence ( J:57631 )

• 50% incidence; causes fatal bleeding in 10% of these cases

respiratory system

increased lung adenoma incidence ( J:57631 )

• 32% incidence

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tuberous sclerosis		DOID:13515	OMIM:PS191100	J:57631

Genotype
MGI:5824119

ht3

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

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

Genotype
MGI:3811791

ht4

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

behavior/neurological

behavior/neurological phenotype ( J:138621 )

N • mice exhibit normal motor skills, exploratory behavior, anxiety and social approach behavior

abnormal contextual conditioning behavior ( J:138621 )

• following contextual conditioning, mice exhibit reduced freezing compared to wild-type mice

• however, treatment with rapamycin re-establishes normal contextual conditioning

abnormal spatial learning ( J:138621 )

• in a hippocampus-dependent version of the Morris water maze test, spatial learning is impaired compared to in wild-type mice

• however, spatial learning in a hippocampus-independent water maze is normal and treatment with rapamycin re-establishes normal spatial learning

• mice exhibit more across-phase errors compared to in wild-type mice in a hippocampus-dependent win-shift version of the eight-arm radial maze

nervous system

nervous system phenotype ( J:138621 )

N • mice exhibit normal basal synaptic transmission, paired-pulse facilitation and early-phase long term potentiation

enhanced long-term potentiation ( J:138621 )

• mice exhibit lowered late-phase threshold for long term potentiation compared to in wild-type mice

• however, treatment with rapamycin re-establishes normal late-phase long term potentiation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tuberous sclerosis		DOID:13515	OMIM:PS191100	J:138621

Genotype
MGI:5824126

cn5

• Allelic Composition: Tsc2^tm1Djk/Tsc2⁺; Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL * C57BL/6 * CBA/JNCrlj

behavior/neurological

abnormal social investigation ( J:217829 )

• in the three-chamber test, mice show impaired preference for sniffing the social target and for social novelty

abnormal response to social novelty ( J:217829 )

• during dyadic encounters, mice spend less time sniffing stimulus mice than control littermates

cellular

abnormal autophagy ( J:217829 )

• mice exhibit high levels of p62/ubiquitin-positive aggregates in cortices at P30, indicating loss of autophagy

nervous system

abnormal dendritic spine morphology ( J:217829 )

• between P21 and P29, basal dendrites from layer V A1/S2 pyramidal neurons exhibit more spines than controls, indicating impaired spine pruning, with only 2% of spines pruned

• treatment with rapamycin does not rescue spine pruning

homeostasis/metabolism

abnormal autophagy ( J:217829 )

• mice exhibit high levels of p62/ubiquitin-positive aggregates in cortices at P30, indicating loss of autophagy

Genotype
MGI:5824122

cx6

• Allelic Composition: Tsc2^tm1Djk/Tsc2⁺; Tg(CAG-EGFP/Map1lc3b)53Nmz/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * C57BL/6NCrlj * DBA/2

cellular

abnormal autophagosome formation ( J:217829 )

• failure of autophagosome induction in neurons

• rapamycin treatment normalizes autophagosome formation in neurons

homeostasis/metabolism

abnormal autophagosome formation ( J:217829 )

• failure of autophagosome induction in neurons

• rapamycin treatment normalizes autophagosome formation in neurons