Analysis Tools
mortality/aging
|
• homozygotes die by 18 days of age (P18), except when hand-fed
|
behavior/neurological
| N |
• homozygotes show normal behavioral responses in tests for negative geotaxis and body positioning in water, indicating that vestibular functions are grossly unaffected
|
|
• by P10, homozygotes exhibit defects in controlling voluntary movements, posture, and balance; these defects increase in severity over time
|
|
• by P15, homozygotes are unable to traverse an elevated 1 inch x 12 inch beam or climb up a 30 cm long knotted rope
|
|
• although normal at birth, homozygotes display progressive ataxia starting at P10
• by P15, homozygotes exhibit crawling forward, as shown by hindlimb print patterns
• ataxia results in frequent falls and rollovers, with a significantly impaired ability to regain the upright position
|
|
• by P10, homozygotes drag their hindlimbs during walking
|
abnormal gait
(
J:58556
)
|
• by P10, homozygotes exhibit a broad-based gait on ink footprints
|
growth/size/body
|
• by P15, homozygotes are noticeably smaller than wild-type mice
|
weight loss
(
J:58556
)
|
• homozygotes fail to gain weight after P10, and are significantly lighter than wild-type mice at time of death
|
nervous system
|
• homozygotes display abnormal fasciculation of cerebellar granule cell axons both in vitro and in vivo
• in vitro, neurites from P5-P6 mutant granule cell clusters appear to extend individually and are diffusely arranged, whereas wild-type granule cell neurites are largely organized into fascicles
• in vivo, P15 homozygotes display a slight but significant (3.8%) reduction in the compaction of parallel fibers within fascicles in the cerebellar ML, as determined by measuring axon areas within fascicles and the spaces between them
|
|
• at P15, mutant cerebella display miguidance of granule cell axon subpopulations
|
|
• at P15, homozygotes display defects in granule cell axon guidance and in dendritic projections from granule and Golgi cells
|
|
• at P13-P16, mutant Purkinje cells display axonal varicosities (swellings), not detected in wild-type mice
• however, no significant differences in Purkinje cell number, positioning, or overall dendritic branching are observed at P13, P15, and P17
|
|
• at P15, homozygotes display reduced granule cell and Golgi cell dendritic expansions relative to wild-type mice
|
|
• at P13 and P17, wild-type Golgi cell dendrites are branched and oriented radially into the ML, whereas mutant Golgi cell dendrite projections are sparse, and the few extending dendrites are often stunted and show little branching
• at P17, only 50% of Golgi cell dendrites extend from the internal granule layer across Purkinje cell bodies into the ML relative to wild-type mice
|
|
• at P15-P16, DiI-labeled wild-type granule cells extend claw-like expansions at the distal ends of their dendrites, whereas mutant granule cells display stubby and underdeveloped distal dendritic expansions associated with a 36% reduction of the granule cell postsynaptic area available for the formation of mossy fibers and Golgi cell synapses
|
|
• at P15, mutant parallel fibers in the outer molecular layer (ML) are misoriented and project 90 degrees to parallel fibers in the inner and middle ML, whereas wild-type parallel fibers are correctly oriented perpendicular to Purkinje cell dendrites within the entire ML
• at P15, homozygotes display a slight but significant (3.8%) reduction in the compaction of parallel fibers within fascicles in the cerebellar ML, as determined by measuring axon areas within fascicles and the spaces between them
|
|
• at P15, the size of mutant cerebella is reduced by 17.5% relative to that of wild-type mice
• however, no significant changes in folia development or laminar organization are observed
|
|
• homozygotes display impaired granule cell and Golgi cell dendritic growth in the cerebellum
|
cellular
|
• homozygotes display abnormal fasciculation of cerebellar granule cell axons both in vitro and in vivo
• in vitro, neurites from P5-P6 mutant granule cell clusters appear to extend individually and are diffusely arranged, whereas wild-type granule cell neurites are largely organized into fascicles
• in vivo, P15 homozygotes display a slight but significant (3.8%) reduction in the compaction of parallel fibers within fascicles in the cerebellar ML, as determined by measuring axon areas within fascicles and the spaces between them
|
|
• at P15, mutant cerebella display miguidance of granule cell axon subpopulations
|
