Phenotypes Associated with This Genotype

Genotype
MGI:5446655

• Allelic Composition: Agtpbp1^pcd/Agtpbp1^pcd
• Genetic Background: involves: C57BL/6J * C57BR/cdJ * DBA/2J

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

vision/eye

decreased amacrine cell number ( J:189268 )

• reduction in the number of calbindin+ amacrine cells at P270, but not earlier time points

abnormal retina rod cell morphology ( J:189268 )

• rod bipolar cells show a progressive loss of dendrites that is first observed at P90 and is complete by P270

retina photoreceptor degeneration ( J:189268 )

• progressive loss of photoreceptor rows is evident by P90, however the outer nuclear layer is not completely lost and at P270, 2-3 rows of photoreceptor cells are retained

abnormal retina inner plexiform layer morphology ( J:189268 )

• smaller terminal end-bulbs and varicosities in the sublamine 5 of the inner plexiform layer are seen from P90

• end-bulbs of axonal terminals are disorganized and smaller

abnormal retina outer nuclear layer morphology ( J:189268 )

• in the oldest mutants (P180 and P270) some horizontal cell somas are abnormally located in the outer nuclear layer

thin retina outer nuclear layer ( J:189268 )

• progressive reduction in thickness due to photoreceptor death

abnormal eye electrophysiology ( J:189268 )

• magnitude of age-related ERG amplitude reduction is more pronounced in mutants than in wild-type mice, especially at later ages

• ERG amplitudes evoked by high intensity stimuli presented to the dark-adapted eye are smaller than in wild-type at all ages tested for the a-wave and at all ages except P45 for the b-wave

• oscillatory potential amplitudes in response to a light flash are different from wild-type

abnormal cone electrophysiology ( J:189268 )

• amplitudes of the cone ERG b-wave is decreased in mutants at P90 and older

• however, no differences from wild-type in cone flicker ERGs are seen

abnormal rod electrophysiology ( J:189268 )

• amplitude of the rod b-wave is reduced in mutants for all postnatal days measured after P90

nervous system

increased neuron apoptosis ( J:263824 )

• TUNEL assays show a significant increase of TUNEL+ apoptotic cells in all three layers of the cerebellum (Purkinje cell-, granule - and molecular layer) from P22 onwards

abnormal cerebellum morphology ( J:263824 )

• mice exhibit progressive cerebellar degeneration

abnormal Purkinje cell morphology ( J:263824 )

• Purkinje cells (PCs) start showing morphological alterations in the main dendrite during the pre-neurodegeneration stage from P15 onwards, with the soma area/size and the dendritic arbor length being the last to be reduced at P22-P30 (neurodegeneration stage)

• however, no defects in PC morphology are detected at P7

Purkinje cell degeneration ( J:263824 )

• mice exhibit loss of Purkinje cells in the cerebellum at P22 and P30

abnormal Purkinje cell dendrite morphology ( J:263824 )

• PCs show a significant reduction in main dendrite length starting at P17 while main dendrite width is already significantly decreased at P15

• in contrast, a significant reduction in dendritic arbor length is observed later -- at P22 and P30 -- when PCs disappear

thin cerebellar molecular layer ( J:263824 )

• a significant reduction in Purkinje cell (PC) dendritic arbor length (measured indirectly via molecular layer thickness) is noted during the neurodegeneration stage (P22 and P30)

decreased amacrine cell number ( J:189268 )

• reduction in the number of calbindin+ amacrine cells at P270, but not earlier time points

abnormal retina rod cell morphology ( J:189268 )

• rod bipolar cells show a progressive loss of dendrites that is first observed at P90 and is complete by P270

retina photoreceptor degeneration ( J:189268 )

• progressive loss of photoreceptor rows is evident by P90, however the outer nuclear layer is not completely lost and at P270, 2-3 rows of photoreceptor cells are retained

behavior/neurological

impaired long-term object recognition memory ( J:263824 )

• in a novel object recognition test, mice show a lack of preference for the new object only at P30, suggesting a deficit in long-term object recognition memory in late neurodegenerative stages

decreased grooming behavior ( J:263824 )

• mice exhibit a significant decrease in grooming time only during neurodegeneration (at P22 and P30, but not earlier)

impaired coordination ( J:263824 )

• mice show impaired motor performance in the rotarod test only during neurodegeneration (at P22 and P30, but not earlier)

decreased vertical activity ( J:263824 )

• mice exhibit a significant decrease in the number of rearings (environmental exploratory behavior) during both pre-neurodegeneration (at P15 and P17) and neurodegeneration (at P30 but, surprisingly, not at P22)

• however, analysis of home-cage behavior shows normal time spent displacing from P15 to P30, suggesting that general movement is unaffected

decreased social investigation ( J:263824 )

• in a social preference test, mice spend the same % of time exploring two chambers that contain either an intruder mouse or an object at all ages (P15, P17, P22 and P30), indicating less preference for social contact due to cerebellar pre-neurodegeneration

cellular

increased neuron apoptosis ( J:263824 )

• TUNEL assays show a significant increase of TUNEL+ apoptotic cells in all three layers of the cerebellum (Purkinje cell-, granule - and molecular layer) from P22 onwards

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa		DOID:10584	OMIM:268000 OMIM:PS268000	J:189268