Phenotypes associated with this allele

• Allele Symbol: Tsc2^tm1Tno
• Allele Name: targeted mutation 1, Tetsuo Noda
• Allele ID: MGI:1926345
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tsc2^tm1Tno/Tsc2^tm1Tno	involves: 129S4/SvJae * C57BL/6J	MGI:2174789
ht2	Tsc2^tm1Tno/Tsc2^+	B6J.129S4-Tsc2^tm1Tno	MGI:5641393
ht3	Tsc2^tm1Tno/Tsc2^+	involves: 129S4/SvJae	MGI:5766244
ht4	Tsc2^tm1Tno/Tsc2^+	involves: 129S4/SvJae * C57BL/6J	MGI:2174790
cn5	Sdcbp^tm1c(KOMP)Wtsi/Sdcbp^+ Tsc2^tm1Tno/Tsc2^+ Tg(Camk2a-cre)2Gsc/0	involves: 129S4/SvJae * C57BL/6N * FVB/N	MGI:5766247

Genotype
MGI:2174789

hm1

• Allelic Composition: Tsc2^tm1Tno/Tsc2^tm1Tno
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:52464 )

• homozygotes start dying at ~E9.0-E9.5, with some embryos surviving to E11.5-E12.5

• 5 of 6 homozygotes are found dead at E11.0-E11.5

nervous system

incomplete rostral neuropore closure ( J:52464 )

• at E9.0-E11.5, ~50% of homozygotes display failure of neural tube closure in the head region

• however, unclosed neural tubes retain normal organization of neuroepithelial structures

cardiovascular system

thick myocardium ( J:52464 )

• at E11.5-E12.5, homozygotes display a thickened myocardium associated with increased cell density

• no differences in cell proliferation of cardiomyocytes in the outer mantle layer or trabeculae are observed despite myocardial anomaly

• a normal myocardium architecture with substantial trabeculation and beating hearts is observed until E9.0-E10.5

abnormal endocardium morphology ( J:52464 )

• at E11.5 and E12.5, mutant endocardia are tightly associated with thickened myocardia

heart hyperplasia ( J:52464 )

• at E11.5-E12.5, homozygotes display a thickened myocardium associated with increased cell density

abnormal heart ventricle morphology ( J:52464 )

• at E11.5 and E12.5, mutant ventricular cavities appear narrowed

growth/size/body

heart hyperplasia ( J:52464 )

• at E11.5-E12.5, homozygotes display a thickened myocardium associated with increased cell density

embryonic growth retardation ( J:52464 )

decreased embryo size ( J:52464 )

• at E10.0 and E11.5, live homozygotes display a reduced body size relative to wild-type embryos

embryo

embryonic growth retardation ( J:52464 )

decreased embryo size ( J:52464 )

• at E10.0 and E11.5, live homozygotes display a reduced body size relative to wild-type embryos

incomplete rostral neuropore closure ( J:52464 )

• at E9.0-E11.5, ~50% of homozygotes display failure of neural tube closure in the head region

• however, unclosed neural tubes retain normal organization of neuroepithelial structures

muscle

thick myocardium ( J:52464 )

• at E11.5-E12.5, homozygotes display a thickened myocardium associated with increased cell density

• no differences in cell proliferation of cardiomyocytes in the outer mantle layer or trabeculae are observed despite myocardial anomaly

• a normal myocardium architecture with substantial trabeculation and beating hearts is observed until E9.0-E10.5

Genotype
MGI:5641393

ht2

• Allelic Composition: Tsc2^tm1Tno/Tsc2⁺
• Genetic Background: B6J.129S4-Tsc2^tm1Tno

behavior/neurological

decreased coping response ( J:221239 )

• immobility time in the tail suspension test is longer than in wild-type mice

• however, in the light/dark box test, time spend in the dark compartment is not different

increased vertical activity ( J:221239 )

• increase in rearing behavior

• treatment with rapamycin attenuates rearing behavior

abnormal social investigation ( J:221239 )

• mice spend a shorter time engaged in active interaction with a novel mouse than wild-type mice

• however, mice are not altered in social dominance, exhibit normal olfaction and exploration towards an inanimate object, and show intact motor and sensory function

• treatment with rapamycin extends the time of active interaction with a novel mouse

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:221239
tuberous sclerosis		DOID:13515	OMIM:PS191100	J:221239

Genotype
MGI:5766244

ht3

• Allelic Composition: Tsc2^tm1Tno/Tsc2⁺
• Genetic Background: involves: 129S4/SvJae

nervous system

nervous system phenotype ( J:222712 )

N • mice exhibit normal evoked EPSC amplitude, mEPSC amplitude, mEPSC frequency, vesicular release probability and number of releasable vesicles

abnormal dendrite morphology ( J:222712 )

• spine density is reduced

abnormal dendritic spine morphology ( J:222712 )

• dendritic protrusion are longer and thinner than in wild-type mice

• increased shaft synapse density compared with wild-type mice

Genotype
MGI:2174790

ht4

• Allelic Composition: Tsc2^tm1Tno/Tsc2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

neoplasm

increased hepatic hemangioma incidence ( J:52464 )

• by 18 months of age, ~80% of heterozygotes develop hepatic hemangiomas that are not macroscopically obvious at 10 months

• hemangiomas develop in both sexes, involve all hepatic lobes, and resemble cavernous hemangiomas composed of a thin layer of endothelium and large blood-filled cavities

increased renal carcinoma incidence ( J:52464 )

• by 6 months, 95% of heterozygotes of both sexes develop spontaneous bilateral and multiple RCs

• by 10 months, virtually all heterozygotes develop RCs which are mostly cystic, with a diameter of 1-2 mm; tubular-type RCs are also observed

• RC development is accelerated by transplacental ENU-treatment of embryos at E14.0 or E15.0

• notably, 4 of 11 larger RCs exhibit loss of the remaining wild-type allele

renal/urinary system

increased renal carcinoma incidence ( J:52464 )

• by 6 months, 95% of heterozygotes of both sexes develop spontaneous bilateral and multiple RCs

• by 10 months, virtually all heterozygotes develop RCs which are mostly cystic, with a diameter of 1-2 mm; tubular-type RCs are also observed

• RC development is accelerated by transplacental ENU-treatment of embryos at E14.0 or E15.0

• notably, 4 of 11 larger RCs exhibit loss of the remaining wild-type allele

liver/biliary system

increased hepatic hemangioma incidence ( J:52464 )

• by 18 months of age, ~80% of heterozygotes develop hepatic hemangiomas that are not macroscopically obvious at 10 months

• hemangiomas develop in both sexes, involve all hepatic lobes, and resemble cavernous hemangiomas composed of a thin layer of endothelium and large blood-filled cavities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tuberous sclerosis		DOID:13515	OMIM:PS191100	J:52464

Genotype
MGI:5766247

cn5

• Allelic Composition: Sdcbp^{tm1c(KOMP)Wtsi}/Sdcbp⁺; Tsc2^tm1Tno/Tsc2⁺; Tg(Camk2a-cre)2Gsc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * FVB/N

nervous system

nervous system phenotype ( J:222712 )

N • mice exhibit normal electrophysiological properties

abnormal dendrite morphology ( J:222712 )

• dendritic protrusions exhibit increased width and density and reduced length compared to in Tsc2^tm1Tno heterozygotes

• however, mice exhibit normal spine and shaft synapse density