Phenotypes Associated with This Genotype

Genotype
MGI:5766909

• Allelic Composition: Car8^wdl/Car8^wdl
• Genetic Background: C57BLKS/J-Car8^wdl/GrsrJ

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

behavior/neurological

abnormal motor learning ( J:230904 )

• motor learning on the rotarod improves at P30 but not over the 12 trials at P90 or P360

tremors ( J:230904 )

• mice develop a severe tremor with age

• as tremor amplitude increases with age, the frequency decreases

ataxia ( J:103673 )

• side-to-side movements are obvious by 2 weeks of age

impaired coordination ( J:230904 )

• motor performance on the rotarod declines with age

• chlorzoxazone treatment improves motor performance on the rotarod, although it does not completely rescue the phenotype to control levels

abnormal gait ( J:81344 )

• this mutant has an odd waddling walk throughout life

hearing/vestibular/ear

abnormal auditory brainstem response ( J:81344 )

• Background Sensitivity: hearing of mutant and control is abnormal by 7 months of age due to C57BLKS/J background

nervous system

abnormal cerebellum morphology ( J:230904 )

• the patterning of the cerebellum into zones is spatially and temporally altered

abnormal cerebellar molecular layer ( J:230904 )

• molecular layer thickness is decreased at P15 and P30, but not at later stages, suggesting a developmental delay

• however, mice do not exhibit cerebellar neurodegeneration or Purkinje cell loss with age

abnormal innervation ( J:230904 )

• the wiring of cerebellar sensory maps is poorly coordinated

• the adult spinocerebellar sensory map is not sharply delineated, with the topography of the afferent map less clear at P90 compared to P30

• cuneocerebellar and spinocerebellar proprioceptive pathways exhibit overlapping domains

• chlorzoxazone does not reconfirgure the miswired cerebellar circuit map

abnormal neuron physiology ( J:230904 )

• Purkinje cell activity is severely impaired, with Purkinje cells firing with long pauses

• Purkinje cells fire erratically on the whole, however they also exhibit higher regularity during firing

• Purkinje cell firing is already compromised in pre-weaned developing pups, with Purkinje cells firing more rapidly and with even less regularity than controls

• chlorzoxazone, a muscle relaxant, corrects several properties of Purkinje cell firing

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome		DOID:0050997	OMIM:PS224050	J:230904