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Phenotypes Associated with This Genotype
Genotype
MGI:6458731
Allelic
Composition
Ap5z1tm1(KOMP)Wtsi/Ap5z1tm1(KOMP)Wtsi
Genetic
Background
involves: 129 * C57BL/6N
Cell Lines EPD0587_5_A05
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ap5z1tm1(KOMP)Wtsi mutation (0 available); any Ap5z1 mutation (32 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
N
• mice exhibit no learning or memory deficits in the Morris water maze paradigm at 6 months of age
• mice develop mild progressive gait abnormalities; the foot-base-angle at toe-off position is significantly reduced at 20 months (55 degrees versus 75 degrees in wild-type controls), but not at 12 or 16 months of age

nervous system
• accumulation of autofluorescent material in pyramidal neurons of layer V of the motor cortex at 8 months of age
• accumulation of autofluorescent material in Purkinje neurons at 8 months of age, with larger clusters of membrane-associated electron-dense deposits of abnormal shape observed ultrastructurally at 20 months of age
• strong activation of astrocytes in the Purkinje cell layer at 20 months of age
• Lamp1-positive axonal swellings in Purkinje cells at 20 months of age
• however, numbers of Purkinje cell bodies and Purkinje cell mitochondria remain normal
• strong activation of astrocytes in the granular cell layer of the cerebellum at 20 months of age
• however, the molecular layer is normal
• strong activation of astrocytes in the granular cell layer of the cerebellum and in the Purkinje cell layer at 20 months of age
• large diameter axons are almost absent in the lumbar corticospinal tract at 20 months of age
• mice show a significant reduction of large diameter axons and various signs of axon degeneration, including abnormal membranous material, in the lumbar corticospinal tract at 20 months of age
• large Lamp1-positive spheroids with a diameter of up to 15 um, resembling lysosomes and autolysosomes, found in the corticospinal tract of the lumbar spinal cord and in the granular layer of the cerebellum at 20 months of age

cellular
• mouse embryonic fibroblasts (MEFs) show a reduction in the relative area of TGN38-positive structures (transGolgi) but not Giantin-positive structures (cisGolgi)
• ultrastructural analysis of Golgi stacks shows an increased number of MEFs with a vesiculated Golgi apparatus
• signals for transGolgi proteins (TGN38 and Glg1) are reduced in Purkinje cells at 20 months, but not at 2 months of age
• mean size of individual Golgi stacks is significantly decreased in MEFs
• upon starvation-induced autophagy, MEFs show a significant increase in autophagosome numbers as well as a significant decrease in autolysosome numbers, indicating a block in autophagic flux under stressed conditions
• upon prolonged starvation (8-9 h), MEFs show impaired autophagic lysosome reformation; number of cells with >5 Lamp1-positive tubules longer than 2 um and level of S6K phosphorylation are significantly lower than in similarly treated wild-type cells
• at 2 months of age (i.e. prior to accumulation of autofluorescent material), numbers of autophagosomes and autolysosomes are significantly increased while lysosomal numbers are normal in Purkinje cell bodies
• at 20 months of age, brains show accumulation of autophagic deposits that are positive for both Lamp1 (a lysosomal membrane protein) and the autophagic cargo receptor p62
• MEFs show impaired cycling of lysosomes from autolysosomes
• analysis of MEFs suggests a trafficking defect from late endosomes to the transGolgi network

homeostasis/metabolism
• upon starvation-induced autophagy, MEFs show a significant increase in autophagosome numbers as well as a significant decrease in autolysosome numbers, indicating a block in autophagic flux under stressed conditions
• upon prolonged starvation (8-9 h), MEFs show impaired autophagic lysosome reformation; number of cells with >5 Lamp1-positive tubules longer than 2 um and level of S6K phosphorylation are significantly lower than in similarly treated wild-type cells
• at 2 months of age (i.e. prior to accumulation of autofluorescent material), numbers of autophagosomes and autolysosomes are significantly increased while lysosomal numbers are normal in Purkinje cell bodies
• at 20 months of age, brains show accumulation of autophagic deposits that are positive for both Lamp1 (a lysosomal membrane protein) and the autophagic cargo receptor p62

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
hereditary spastic paraplegia 48 DOID:0110800 OMIM:613647
J:283611


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/23/2021
MGI 6.16
The Jackson Laboratory