All Phenotypes Atp1b2<tm1Msch> MGI Mouse

postnatal lethality, complete penetrance ( J:21121 )

• homozygotes died at postnatal days P17 or P18

abnormal food intake ( J:21121 )

• as motor incoordination progressesed, mutants were no longer able to feed and drink

• efforts to keep the animals viable by artificial feeding failed

impaired righting response ( J:21121 )

• at P15, mutants showed reduced righting behavior and orientation when lifted by tail and dropped gently into the cage

tremors ( J:21121 )

• the hind limbs became tremorous and mutants were unable to remain in an upright position

impaired coordination ( J:21121 )

• mutants fell onto their side and paused for a few seconds before they stood up on their feet and started moving

• mutants lying on their side still showed normal grasping reflexes and responded to sound

forelimb paralysis ( J:21121 )

• after P15, mutants developed forelimb paralysis and were unable to hold their heads in a normal position

vision/eye phenotype ( J:21121 )

N

• the optic nerves appeared histologically normal

• there were no signs of degeneration in the vicinity of blood vessels

• compacted myelin, retinal ganglion cell axons, and astrocytic endfeet abutting onto blood vessels or forming the glial limiting membrane at the outer surface of the nerve appeared normal

abnormal retina photoreceptor morphology ( J:21121 )

short photoreceptor inner segment ( J:21121 )

• the length of inner segments of photoreceptor cells was significantly reduced

short photoreceptor outer segment ( J:21121 )

• the length of outer segments of photoreceptor cells was significantly reduced

retina photoreceptor degeneration ( J:21121 , J:74968 )

• degenerating photoreceptor cell bodies were observed at the ultrastructural level (J:21121)

• the retinal photoreceptor cells developed normally during the first week of life (J:74968)

• a slightly increased density of degenerating retinal photoreceptor cells was evident at P9, and numerous degenerating photoreceptor cells were observed at P16 (J:74968)

• TUNEL analysis and electron microscopy revealed apoptosis of degenerating photoreceptor cells (J:74968)

• at P16, extensive degeneration of photoreceptor cells was correlated with high levels of GFAP in retinal astrocytes and with expression of GFAP by Muller cells (J:74968)

• no degeneration was observed in other retinal cell types (J:74968)

• no signs of glial cell death in the optic nerve (J:74968)

eyelids fail to open ( J:21121 )

• homozygotes opened their eyes at the correct age, but most of them kept them closed when the behavioral abnormalities became apparent

thin retina outer nuclear layer ( J:21121 )

• the outer nuclear layer of the retina was reduced in thickness

retina outer nuclear layer degeneration ( J:21121 )

• the outer nuclear layer of the retina contained numerous degenerating cells

retina degeneration ( J:21121 )

• in contrast to the brain stem, retinal blood vessels were not associated with degenerating cellular elements

nervous system phenotype ( J:21121 )

N	• brain homogenates of 16-17-day-old mutants displayed normal Na+, K+-ATPase pump activity

enlarged lateral ventricles ( J:21121 )

• the lateral ventricles were significantly enlarged

enlarged third ventricle ( J:21121 )

• the third ventricles were significantly enlarged

abnormal brainstem morphology ( J:21121 )

• in the mutant brain stem, swollen cellular processes and vacuoles were observed in close association with blood vessels; these vacuoles probably resulted from swelling and subsequent degeneration of astrocytic endfeet

• similar vacuolated structures were noted in the thalamus, striatum, and spinal cord

abnormal cerebellar granule layer morphology ( J:21121 )

• in contrast to the brain stem, blood vessels of the cerebellar cortex were not associated with degenerating cellular elements

• however, some degenerating Purkinje cells and some small-sized degenerating cells in the internal granular layer were observed