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Phenotypes Associated with This Genotype
Genotype
MGI:3714016
Allelic
Composition
Ptentm2Mak/Ptentm2Mak
Tg(Gfap-cre)1Sbk/0
Genetic
Background
involves: 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm2Mak mutation (4 available); any Pten mutation (78 available)
Tg(Gfap-cre)1Sbk mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• all die by 29 weeks of age, with an average of 10 weeks (J:75500)

nervous system
• 11 of 25 develop seizures by 9 weeks of age; symptoms include episodes of front-paw tremors followed by spasms of hind legs
• beyond 6 weeks, mice exhibit epileptiform activity associated with tonic-clonic seizures
• mice exhibit subclinical electrographic seizures lasting for at least 10 seconds largely without obvious behavioral changes unlike in wild-type mice
• at 6 weeks, two of seven mice display behavioral changes characteristic of tonic-clonic activity
• at 9 weeks, three of seven mice display behavioral changes characteristic of tonic-clonic activity
• mice exhibit isolated interictal spikes, short trains of repetitive spike lasting less than 5 seconds and long runs of repetitive spikes lasting between 5 and 10 seconds
• spike waves are more frequent at 9 weeks than at 6 weeks
• however, treatment with rapamycin reduces the severity of electrographic abnormalities
• often see hydrocephalus of the lateral ventricles
• 43% increased in brain size at 10-14 weeks of age, but not at 4 weeks (J:75500)
• variable with apparent enlargement of cortical, hippocampal and cerebellar structures (J:149829)
• prominent astrogliosis in the hippocampus and the sub-pial surface
• disorganization of the dentate gyrus at 10 weeks of age, characterized by marked undulation of the granule-cell layer
• intercellular spaces between granule-cell bodies, containing thick neuronal dendrites and astrocytes are expanded
• granule cells of the dentate gyrus have a greater surface area (are enlarged)
• sclerosis of the pyramidal cell layer of the CA3
• reduction in pyramidal cell density of the cornu ammonis
• enlarged cerebellum
• thickened cerebellar folia
• multifocal persistence of the external granular cell layer at the pial surface
• those Purkinje cells remaining are atrophic or dysplastic as indicated by dendritic coarsening and axonal swelling
• partial loss of Purkinje cells
• soma size is increased in granule neurons at 10 weeks of age
• mutants exhibit heterotopic neuronal clusters scattered in the molecular layer
• the molecular layer is thickened, especially at sites of heterotopic lesions
• disorganization, dysplasia, gliosis and elevated myelination in the molecular layer
• gliosis in the molecular layer
• astrogliosis is visible in close proximity to the affected heterotopic neurons in the cerebellum and in the hippocampus and the sub-pial surface
• cortical Pten-negative neurons are hypertrophic
• at P12, soma size of Pten-negative neurons is increased 1.7-fold compared with wild-type neurons
• adult Pten-negative neurons are larger than in wild-type mice
• however, Pten-negative pyramidal neurons do not exhibit an increase in size with age and treatment with rapamycin suppresses neuron hypertrophy

behavior/neurological
• develop sudden lethargy at 9 weeks of age
• 13 of 25 develop ataxia by 9 weeks of age (J:75500)
• 11 of 25 develop seizures by 9 weeks of age; symptoms include episodes of front-paw tremors followed by spasms of hind legs
• beyond 6 weeks, mice exhibit epileptiform activity associated with tonic-clonic seizures
• mice exhibit subclinical electrographic seizures lasting for at least 10 seconds largely without obvious behavioral changes unlike in wild-type mice
• at 6 weeks, two of seven mice display behavioral changes characteristic of tonic-clonic activity
• at 9 weeks, three of seven mice display behavioral changes characteristic of tonic-clonic activity
• mice exhibit isolated interictal spikes, short trains of repetitive spike lasting less than 5 seconds and long runs of repetitive spikes lasting between 5 and 10 seconds
• spike waves are more frequent at 9 weeks than at 6 weeks
• however, treatment with rapamycin reduces the severity of electrographic abnormalities

neoplasm
• brain lesions are categorized as hamartomas
• however, do not develop glioblastomas between 4-19 weeks of age

growth/size/body
• variable with apparent enlargement of cortical, hippocampal and cerebellar structures (J:149829)

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
brain disease DOID:936 J:149829
Cowden syndrome DOID:6457 OMIM:PS158350
J:75500


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
06/23/2022
MGI 6.20
The Jackson Laboratory