Phenotypes Associated with This Genotype

Genotype
MGI:5660888

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

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

behavior/neurological

abnormal behavior ( J:109635 )

• mutants are unusually resistant to handling by 6 weeks of age

impaired spatial learning ( J:109635 )

• in the Morris water maze, mutants learn the visible platform task as well as controls but show a trend toward slower acquisition

• in the submerged platform Morris water maze, mutants do not learn as quickly as controls, showing increased latency and longer distance traveled to reach the platform

• in the probe trial, mutants show no preference for time spent in each quadrant unlike controls which spend more time in the target quadrant

increased anxiety-related response ( J:109635 )

• mice show increased anxiety-like behavior in the open field where they spend less time in the center zone and show a lower ratio of center versus periphery time

• in the dark/light apparatus, mutants show longer latencies to enter the light side, spending most of their time on the dark side

• however, in the elevated plus maze, mutants do not show anxiety-like behavior

increased thigmotaxis ( J:109635 )

• mice exhibit a greater tendency to swim along the edge of the Morris water maze

increased startle reflex ( J:109635 )

• mutants exhibit increased initial startle responses to a 120 dB white noise stimulation

• however, mice show similar startle responses as controls upon repeated startle stimulation indicating normal habituation

increased locomotor activity ( J:109635 )

• mutants exhibit normal locomotor activity in less stressful environments but hyperactivity under more stressful conditions

• mice are hyperactive in the bright environment of the open field, traveling further at an increased average speed

• however, in the dark/light boxes and in the enclosed, darker environments of the locomotor apparatus, locomotor activity is normal

increased stereotypic behavior ( J:109635 )

• mice exhibit normal coordination on the accelerating rotarod test during initial trials, however they perform better during subsequent trials indicating better performance in a repetitive behavior

abnormal maternal nurturing ( J:109635 )

• mortality of pups by P5 from mutant females fertilized by wild-type males is increased, indicating defects in maternal care

abnormal nest building behavior ( J:109635 )

• mutants show little nest forming activity

abnormal sexual interaction ( J:109635 )

• no naive mutant males make female mice pregnant and active sexual behavior is not seen by males, however fertility of males is not analyzed

abnormal social investigation ( J:109635 )

• mice show decreased social interaction and abnormal social learing in several tests without change in novel object exploration, preference for social novelty, or olfaction

sporadic seizures ( J:109635 )

• 6 of 52 mutants exhibited sporadic seizures during testing

• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted

• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds

• sound and tactile stimuli do not induce seizures

growth/size/body

megacephaly ( J:109635 )

• mice show progressive macrocephaly, confined to the forebrain (cortex and hippocampus)

nervous system

sporadic seizures ( J:109635 )

• 6 of 52 mutants exhibited sporadic seizures during testing

• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted

• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds

• sound and tactile stimuli do not induce seizures

increased brain weight ( J:109635 )

• progressive increase in brain weight after 2 months of age

abnormal hippocampus CA1 region morphology ( J:109635 )

• aging mice show compression or absence of the CA1 region

abnormal dentate gyrus morphology ( J:109635 )

• aging mice show foliation of the dentate gyrus

• disorganized dentate gyrus granular layer

• progressive increase in the thickness of MAP2+ dentate molecular layer

increased dentate gyrus size ( J:109635 )

• progressive enlargement with age

abnormal hippocampal mossy fiber morphology ( J:109635 )

• dentate gyrus shows progressive enlargement of the mossy fiber tract

• mice show elongated and dispersed mossy fiber tract from the granular layer of the dentate gyrus

thickened cerebral cortex ( J:109635 )

abnormal innervation ( J:109635 )

• ectopic neuronal processes extending from the cell bodies into the dentate gyrus polymorphic layer are seen in the dentate gyrus at 3 months of age

abnormal dendrite morphology ( J:109635 )

• dendritic hypertrophy and ectopy in adult dentate gyrus

• at 8 months of age, dendrites of ectopic neurons extending into the dentate gyrus polymorphic layer are longer and thicker and dendrites extending into the molecular layer are thicker

• at 8 months, dendritic arbors in the molecular layer of the dentate gyrus are increased in length

increased dendritic spine density ( J:109635 )

• 24.9% increase in dendritic spine density within the molecular layer of the dentate gyrus

abnormal synapse morphology ( J:109635 )

• synapses of the dentate gyrus are abnormal

• mossy fiber synapses span a larger area

abnormal synaptic vesicle number ( J:109635 )

• the dentate gyrus inner molecular layer shows an increase in presynaptic vesicle number

ectopic neuron ( J:109635 )

• at 8 months of age, ectopic neuronal processes extend into the polymorphic and molecular layers of the dentate gyrus

neuron hypertrophy ( J:109635 )

• Pten-negative neurons are larger than Pten-positive neurons at 4 weeks of age

• progressive increase in neuronal soma diameter indicating soma hypertrophy

reduced sensorimotor gating ( J:109635 )

• sensorimotor gating is impaired

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
macrocephaly-autism syndrome		DOID:0060867	OMIM:605309	J:109635