All Phenotypes Prkab1<Gt(RRR454)Byg> MGI Mouse

postnatal lethality, complete penetrance ( J:146618 )

• mice die by P21

seizures ( J:146618 )

• mice exhibit seizures that recur within less than 10 minutes

abnormal neuron differentiation ( J:146618 )

• at E14.5, fewer cells in the forebrain undergoing mitosis and more Tuj1+ and Oligo2+ cells undergoing apoptosis compared to in wild-type mice

• large numbers of cells in the forebrain at E14.5 and cerebellum at P7 undergo apoptosis unlike in wild-type mice

• however, no cell death is observed in astrocytes at P7 and E18.5

• in culture, neurospheres exhibit increased cell death comapre4d to wild-type cells

• in culture, neurospheres produce fewer Tuj1+ neurons and O4+oligodendrocytes compared to wild-type neurospheres

• in culture, neurosphere differentiation into GFAP+ astrocytes is abnormal

• cultured cerebellar granule cell precursors from P2 cerebellum exhibit impaired reaggregate formation and neurite projection compared to wild-type cells

• however, cultured neurospheres transfected with a constitutively active Prkab1 exhibit rescued self-renewal and cell survival

abnormal neuronal precursor proliferation ( J:146618 )

• at E14.5, fewer cells in the forebrain undergoing mitosis and more Tuj1+ and Oligo2+ cells undergoing apoptosis compared to in wild-type mice

• at E18.5, 22% fewer mitotic cells around the lateral ventricles compared to in wild-type mice

• at P7, fewer cells in the dentate gyrus and cerebellum undergoing mitosis compared to in wild-type mice

• in culture, neurospheres are smaller than those that develop from wild-type cells

• proliferation of neuronal precursor cells is half of wild-type

• neuronal precursor cells exhibit defective mitosis in the G2M phase compared to wild-type cells

decreased brain size ( J:146618 )

• at E18.5 and P14, brain size is reduced by 50% compared to in wild-type

abnormal dentate gyrus morphology ( J:146618 )

• the dentate gyrus is nearly completely lost

loss of hippocampal neurons ( J:146618 )

• mice exhibit between 35% and 65% loss in cortical and granule neurons in the dentate gyrus compared to in wild-type mice

abnormal cerebral cortex morphology ( J:146618 )

• reduction in the cerebral cortex results in improper cortical fusion and exposure of the superior and inferior colliculi unlike in wild-type mice

abnormal cerebellum morphology ( J:146618 )

• mice exhibit disordered laminar organization in the cerebellum unlike in wild-type mice

absent cerebellar granule layer ( J:146618 )

cerebellum atrophy ( J:146618 )

• severe cerebellar atrophy

brain vacuoles ( J:146618 )

• mice exhibit spongiform vacuolation

abnormal astrocyte morphology ( J:146618 )

• the number of astrocytes is increased compared to in wild-type mice

• at E18.5, the number of GFAP+ migrating astrocytes is greater than in wild-type mice

astrocytosis ( J:146618 )

• extensive

decreased oligodendrocyte number ( J:146618 )

• at P14, mice exhibit a 75% to 80% loss in oligodendrocytes compared to in wild-type mice

abnormal axon morphology ( J:146618 )

• mice exhibit loss of white matter axonal projections unlike in wild-type mice

abnormal dendrite morphology ( J:146618 )

• mice exhibit widespread loss of dendritic processes unlike in wild-type mice

decreased neuron number ( J:146618 )

• mice exhibit loss of neurons in the cortex, cerebellum, dentate gyrus, and hypothalamus compared to in wild-type mice

decreased cerebellar granule cell number ( J:146618 )

• mice exhibit between 35% and 65% loss in cortical and granule neurons in the inner granule layer compared to in wild-type mice

abnormal optic nerve morphology ( J:146618 )

• translucent and hypomyelinated

optic nerve hypoplasia ( J:146618 )

• 30% thinner than in wild-type mice

abnormal myelination ( J:146618 )

• mice exhibit severe hypomyelination throughout the brain, particularly in the corpus callosum and striatum, compared to in wild-type mice

• the optic nerve is hypomyelinated

tremors ( J:146618 )

• severe

ataxia ( J:146618 )

• mice exhibit an ataxic gait

seizures ( J:146618 )

• mice exhibit seizures that recur within less than 10 minutes

decreased body weight ( J:146618 )

• mice are emaciated at P14

slow postnatal weight gain ( J:146618 )