Phenotypes Associated with This Genotype

Genotype
MGI:5307916

cn3

• Allelic Composition: Cacna1a^tm1Kano/Cacna1a^tm1Kano; Grid2^tm1(cre)Mwa/Grid2⁺
• Genetic Background: involves: C57BL/6N

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

nervous system

abnormal Purkinje cell morphology ( J:180582 )

• soma surface of Purkinje cells (PCs) is rough in contrast to smooth surface in controls

Purkinje cell degeneration ( J:180582 )

• Purkinje cell (PC) numbers decrease starting at P21 and continue to decrease; soma and dendrites of PCs show degenerative features like somatic shrinkage, darkened cytoplasm, increased electron-dense materials and accumulation of mitochondria with few soma or dendrites found in the cerebellar cortex by P35

• PC degeneration is more apparent in anterior lobules than posterior lobules; remaining PCs display striped or banded patterns

abnormal Purkinje cell dendrite morphology ( J:180582 )

• surface of Purkinje cell dendrites is rough with protrusion of spines or spine-like processes that form asymmetrical synapses with nerve terminals

• number of spines per 1 um of dendrites (>2 um in caliber) is significantly increased compared to controls

abnormal cerebellar molecular layer ( J:180582 )

• terminal profiles in the neuropil are enlarged and in contact with multiple Purkinje cell (PC) spines, often engulfing them, resulting in highly convoluted terminal contours; however density of asymmetrical synapses on PCs is significantly decreased relative to controls

• parallel fiber (PF) terminals are sparse, with many appearing coarse and intense on basis of Slc17a7 (VGluT1) immunolabeling; some PF-PC synapses show a 1:1 contact between PF terminals and PC spines but other exhibit large PF terminals forming multiple contacts

• climbing fiber (CF) terminals are irregular in shape and size; innervation stops midway along proximal dendrites; number of perisomatic CF terminals per unit area of somatic surface is markedly higher than in controls on basis of Slc17a6 (VGluT2) immunolabeling

• regressed innervation territory of climbing fibers on Purkinje cells down to basal dendrites and somata is observed in mutants resulting in multiple innervation

small cerebellum ( J:180582 )

• cerebellum is smaller than in controls at P21, but foliation and laminar organization as well as dendritic branching appear normal

• cerebellum size is reduced even more from P21 to adult

abnormal excitatory postsynaptic current amplitude ( J:180582 )

• unitary EPSCs fromPurkinje cells have larger and more variable amplitudes than controls

increased neurotransmitter release ( J:180582 )

• paired-pulse ratio at short interpulse intervals is smaller than in controls indicating a higher presynaptic release probability