Phenotypes Associated with This Genotype

Genotype
MGI:5749268

• Allelic Composition: Zfyve26^tm1.1Cahb/Zfyve26^tm1.1Cahb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6

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

Abnormal gait of a Zfyve26^tm1.1Cahb/Zfyve26^tm1.1Cahb mouse walking on a beam

growth/size/body

decreased body weight ( J:223127 )

• although normal up to 8 months of age, body weight is reduced by 17% at 16 months of age

enlarged urinary bladder ( J:223127 )

• enlarged bladder at post mortem after 16 months of age

behavior/neurological

behavior/neurological phenotype ( J:223127 )

N • no obvious learning and memory deficits noted in the Morris water maze at 5 months of age

ataxia ( J:223127 )

• progressive spastic and ataxic gait disorder

impaired coordination ( J:223127 )

• progressive decline in beam walking performance, starting at 8 months of age

• significantly impaired motor coordination at 16 months, when homozygotes fall off the beam in about 1 of 3 trials

abnormal posture ( J:223127 )

• at 16 months of age

abnormal gait ( J:223127 )

• progressive gait disorder and motor deficits starting at 12 months of age, as quantified by the foot-base-angle at toe-off positions of the hindpaws

• at 16 months of age, the foot-base-angle is reduced to ~50 degrees versus ~75 degrees in wild-type mice

nervous system

delayed axon extension ( J:223127 )

• after 4 days in culture, the length of outgrowing axons as well as the bidirectional axonal transport rate of mitochondria are significantly decreased in mutant embryonic motoneurons

• however, axonal branching is not altered in cultured motoneurons

decreased brain weight ( J:223127 )

• significantly reduced brain weight at 16 months of age

Purkinje cell degeneration ( J:223127 )

• Purkinje cells severely reduced to 26% of wild-type controls at 16 months of age, consistent with the ataxic gait disorder

brain atrophy ( J:223127 )

• significantly reduced brain size at 16 months of age

• however, normal brain structures and weight at 2 months of age

• no thinning of the corpus callosum at 16 months of age

astrocytosis ( J:223127 )

• marked astrogliosis in the deep layers V and VI of the motor cortex and in the cerebellum at 16 months, but not at 2 months of age

• clear activation of astrocytes in the spinal cord (mainly in the white matter) at 16 months, but not at 2 months of age

• however, no astrogliosis observed in the hippocampus or the olfactory bulb

motor neuron degeneration ( J:223127 )

• significantly reduced number of neurons in deep layers V and VI of the motor cortex at 16 months of age

• however, normal number of neurons in the motor cortex at 2 and 8 months of age

• no neurodegeneration observed in the hippocampus or the olfactory bulb

axon degeneration ( J:223127 )

• axonal degeneration in the corticospinal tract at 8 months, but not at 2 months of age

• large diameter axons are almost absent from horizontal lumbar spinal cord sections at 16 months of age

renal/urinary system

enlarged urinary bladder ( J:223127 )

• enlarged bladder at post mortem after 16 months of age

abnormal urinary bladder physiology ( J:223127 )

• dysfunction of the bladder at 16 months of age

cellular

abnormal lysosome morphology ( J:223127 )

• pathological accumulations of autofluorescent, electron-dense material in lysosomal structures of mutant neurons, preceding degeneration of cortical motoneurons and Purkinje cells

delayed axon extension ( J:223127 )

• after 4 days in culture, the length of outgrowing axons as well as the bidirectional axonal transport rate of mitochondria are significantly decreased in mutant embryonic motoneurons

• however, axonal branching is not altered in cultured motoneurons

abnormal lysosome physiology ( J:223127 )

• altered composition/function of lysosomes

• increased enzymatic activities of lysosomal enzymes beta-hexosaminidase and beta-galactosidase in brain at 16 months, but not at 2 months of age

skeleton

kyphosis ( J:223127 )

• kyphosis of the spine at 16 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spastic paraplegia 15		DOID:0110768	OMIM:270700	J:223127