Phenotypes associated with this allele

• Allele Symbol: Agtpbp1^pcd
• Allele Name: Purkinje cell degeneration
• Allele ID: MGI:1856535
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Agtpbp1^pcd/Agtpbp1^pcd	B6.BR-Agtpbp1^pcd/J	MGI:4360641
hm2	Agtpbp1^pcd/Agtpbp1^pcd	involves: C57BL/6J * C57BR/cdJ * DBA/2J	MGI:5446655
hm3	Agtpbp1^pcd/Agtpbp1^pcd	involves: C57BR/cdJ	MGI:4835174
hm4	Agtpbp1^pcd/Agtpbp1^pcd	involves: C57BR/cdJ * CBA	MGI:2175210

Genotype
MGI:4360641

hm1

• Allelic Composition: Agtpbp1^pcd/Agtpbp1^pcd
• Genetic Background: B6.BR-Agtpbp1^pcd/J

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

Agtpbp1^pcd/Agtpbp1^pcd mouse

vision/eye

abnormal photoreceptor connecting cilium morphology ( J:249732 )

• progressive tubulin hyperglutamylation in cilium microtubles from age P30

• cilia 36 % shorter at age P30

• normal tubulin glutamylation in cilium microtubles at age P19

• normal cilia length at age P19

retina photoreceptor degeneration ( J:249732 )

• progressive tubulin hyperglutamylation in microtubles of photoreceptor connecting cilia between inner and outer segments from age P30

• photoreceptor connecting cilia 36 % shorter at age P30

• normal tubulin glutamylation in microtubles of photoreceptor connecting cilia at age P19

• normal photoreceptor connecting cilia length at age P19

nervous system

abnormal photoreceptor connecting cilium morphology ( J:249732 )

• progressive tubulin hyperglutamylation in cilium microtubles from age P30

• cilia 36 % shorter at age P30

• normal tubulin glutamylation in cilium microtubles at age P19

• normal cilia length at age P19

retina photoreceptor degeneration ( J:249732 )

• progressive tubulin hyperglutamylation in microtubles of photoreceptor connecting cilia between inner and outer segments from age P30

• photoreceptor connecting cilia 36 % shorter at age P30

• normal tubulin glutamylation in microtubles of photoreceptor connecting cilia at age P19

• normal photoreceptor connecting cilia length at age P19

cellular

abnormal photoreceptor connecting cilium morphology ( J:249732 )

• progressive tubulin hyperglutamylation in cilium microtubles from age P30

• cilia 36 % shorter at age P30

• normal tubulin glutamylation in cilium microtubles at age P19

• normal cilia length at age P19

Genotype
MGI:5446655

hm2

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

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

Genotype
MGI:4835174

hm3

• Allelic Composition: Agtpbp1^pcd/Agtpbp1^pcd
• Genetic Background: involves: C57BR/cdJ

nervous system

abnormal cochlear VIII nucleus morphology ( J:121314 )

• few cartwheel cells in the dorsal cochlear nucleus

decreased Purkinje cell number ( J:121314 )

• few Purkinje cell

Genotype
MGI:2175210

hm4

• Allelic Composition: Agtpbp1^pcd/Agtpbp1^pcd
• Genetic Background: involves: C57BR/cdJ * CBA

behavior/neurological

ataxia ( J:5613 )

• age of onset, 3 - 4 weeks

nervous system

abnormal thalamus morphology ( J:5613 )

• thalamic neuronal degeneration, age of onset 50 - 60 days

abnormal olfactory bulb morphology ( J:5613 )

• olfactory mitral cell degeneration, slow and progressive

abnormal cerebellar Purkinje cell layer ( J:106414 , J:23733 )

• symmetrical regions of more resistant cells but most disappear eventually (J:106414)

• climbing fibers never contact Purkinje cells (J:23733)

Purkinje cell degeneration ( J:5613 )

• age of onset, 15 - 18 days

abnormal Purkinje cell dendrite morphology ( J:23733 )

• atrophic dendritic trees

decreased Purkinje cell number ( J:106414 )

• cell loss begins at 3 weeks of age and progresses rapidly

• about 1% of initial population remains at 2 months of age

abnormal cerebellar granule layer morphology ( J:5613 )

• granule cell degeneration, partial loss following Purkinje cell degeneration

retina photoreceptor degeneration ( J:5613 )

• photoreceptor cell degeneration, age of onset, 18 - 25 days

• complete over the course of 1 year

vision/eye

retina photoreceptor degeneration ( J:5613 )

• photoreceptor cell degeneration, age of onset, 18 - 25 days

• complete over the course of 1 year

reproductive system

abnormal male germ cell morphology ( J:5613 )

♂ • of the few sperm found, these were degenerated

oligozoospermia ( J:5613 )

♂

asthenozoospermia ( J:5613 )

♂

reduced female fertility ( J:5613 )

♀ • females were poor breeders

male infertility ( J:5613 )

♂

cellular

abnormal male germ cell morphology ( J:5613 )

♂ • of the few sperm found, these were degenerated

oligozoospermia ( J:5613 )

♂

asthenozoospermia ( J:5613 )

♂