Phenotypes associated with this allele

• Allele Symbol: Cacna1a^tm1Kano
• Allele Name: targeted mutation 1, Masanobu Kano
• Allele ID: MGI:5140539
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cacna1a^tm1Kano/Cacna1a^tm1Kano Grid2^tm1(cre)Mwa/Grid2^+	involves: C57BL/6 * C57BL/6N	MGI:5140544
cn2	Cacna1a^tm1Kano/Cacna1a^tm1Kano Grin2c^tm2(icre)Mwa/Grin2c^+	involves: C57BL/6N	MGI:5307915
cn3	Cacna1a^tm1Kano/Cacna1a^tm1Kano Grid2^tm1(cre)Mwa/Grid2^+	involves: C57BL/6N	MGI:5307916

Genotype
MGI:5140544

cn1

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

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

nervous system

abnormal neuron morphology ( J:173318 )

• regression of surplus climbing fibers (CFs) is severely impaired compared to in control mice

• from P5 to P7, the bias toward strengthening single CFs is impaired compared to in control mice

• multiple CFs translocate to dendrites and impairs elimination of CF synapses from the soma unlike in control cells

abnormal CNS synaptic transmission ( J:173318 )

• at P5 to P6, Purkinje cells (PCs) in cerebellar slices exhibit reduced calcium currents compared with control cells

• PCs lack P/Q-type voltage-dependent calcium channel (VDCC) compared with control cells

• climbing fiber (CF)-induced calcium transients in PCs are reduced compared to in control cells

• however, mice exhibit normal P/Q channel contribution to CF to PC synaptic transmission and spontaneous inhibitory postsynaptic currents at P6 to P7 and P10

abnormal excitatory postsynaptic currents ( J:173318 )

• from P5 to P8, the fractions of multiple CF-EPSCs remains unchanged unlike in control mice

prolonged excitatory postsynaptic current decay time ( J:173318 )

• in climbing fiber cells

prolonged excitatory postsynaptic current rise time ( J:173318 )

• in climbing fiber cells

Genotype
MGI:5307915

cn2

• Allelic Composition: Cacna1a^tm1Kano/Cacna1a^tm1Kano; Grin2c^tm2(icre)Mwa/Grin2c⁺
• Genetic Background: involves: C57BL/6N

nervous system

nervous system phenotype ( J:180582 )

N • size and histology of cerebellum is normal; thickness and cell density of granular layer is normal

N • proximal dendrites and soma of Purkinje cells are normal; parallel fiber terminals are normal in size and do not display multiple contacts, and climbing fiber terminals do not show regressed innervation territory as observed in Purkinje cell specific-Cacna1a mutants

Genotype
MGI:5307916

cn3

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

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