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. 2025 Mar 25;19(1):2480089. doi: 10.1080/19336950.2025.2480089

Table 1.

Summary of phenotypes from previously published mouse models used to study the effects of the Cav channel complex in the mouse retina.

Gene Mouse model Phenotype Reference
CACNA1F Cav1.4-Knock out

  • Reduced Cav1.4 protein levels

 [64,81–85,101]
   

  • Lacking invaginating postsynaptic neurons, Floating ribbons

  
  (Cacna1fΔEx14–17)

  • ERG: reduced a-wave; missing b-wave

  
  (Cacna1fΔEx7)

  • Reduced responsiveness of ganglion cells

  
   

  • Absence of visually evoked activation in the cortex

  
   

  • HC and BC neurite sprouting, only immature (punctate) ribbons

  
  (nob2)

  • ERG: detectable but reduced b-wave and oscillatory potentials; a-wave normal

 [86,102]
   

  • Normal optokinetic response

  
   

  • B-wave under dark adapted conditions is similar to that seen in CSNB2 patients with pathogenic CACNA1F variants

  
  Cav1.4-Knock in

  • ERG: reduced b-wave amplitude at the highest light intensity.

 [27,28]
  (Cav1.4-G369i)

  • Vision-guided behavior: normal at photopic conditions, but not scotopic.

  • Increased protein appearance: mGluR6, TRPM1; Cav1.4 and bassoon.

  
   

  • HC and BC neurite sprouting

  
   

  • Larger cone synapses; shorter and floating ribbons in rods and larger ribbons in cones; more vesicles in cone ribbons

  
  (Cav1.4-I756T)

  • ERG: reduced a wave, reduced b-wave at photopic and scotopic responses

 [64,85,87–89]
   

  • Altered ganglion cell response, HC response from cone synapses: normal

  
   

  • Reduction in expression of Cacna1f, β2 and α2δ-4

  
   

  • Thinner ONL → progressive retinal degeneration,

  
   

  • Shorter cones, HC and BC neurite sprouting, develop ectopic neurites

  
   

  • HC maintained their synaptic contacts with cones.

  
   

  • P13: Ribbon structure similar to WT, P15: many ribbons immature, but some mature, floating ribbons in cones.

  
   

  • ERG similar in human patients, however retinal degeneration was not shown in humans.

  
CACNB2 β2-Knock out

  • ERG: B-wave amplitude reduced, but retain some level of signal transmission in rods; a-wave remained unaffected.

 [95,96]
   

  • Reduced Cav1.4 protein levels

  
   

  • Thinner OPL and dot-like ribbon synapse proteins (e.g. Cav1.4, ribeye, and β-dystroglycan)

  
   

  • NF200 staining indicated HC axon sprouting

  
   

  • Ultrastructural analysis of rods showed a loss of ribbon-shaped structures, no invaginations of second-order neurons; However, cone synapses were largely spared; immature ribbons in rod photoreceptors.

  
CACNA2D4 α2δ-4-Knock in

  • ERG: Reduction in the scotopic a- and b-wave

 [18,68]
  (c.2367insC/c.2451insC)

  • Decreased α2δ-4 protein levels; truncation of the α2δ-4 protein; Increased the proportion of Ex25b transcripts

  
  α2δ-4-Knock out

  • ERGs: no photopic b-wave, no scotopic b-wave

 [92]
   

  • Diminished presynaptic Ca2+ signals in rod spherules

  
   

  • Longer time to detect the escape platform in a visually guided swim assay under photopic conditions.

  
   

  • Decreased α2δ-4, PSD-95 protein levels

  
   

  • Gradual loss of presynaptic calcium channels in both rod and cone photoreceptors.

  
   

  • Cav1.4 labeling punctate at P10 and P14, but present in the OPL during early developmental stages. However, by P21, the Cav1.4 labeling was indistinguishable to WT; Normally distributed ribbons

  
   

  • Cones: α2δ-4 essential for Ca1.4 channel function, but not required for ribbon organization or synaptic transmission.

  
   

  • EM: Most cone ribbons lacked a synaptic triad and that cone bipolar cells were sprouting.

  
  α2δ-4-Knock out

  • ERG: normal a- wave; no scotopic b-wave, reduced photopic b-wave

 [91,110]
  (α2δ-4ΔEx8)

  • Longer time to detect the escape platform in a visually guided swim assay under photopic conditions.

  
   

  • Reduced Ca2+ signals in rod photoreceptors

  
   

  • No light-evoked responses in ON RBC and ON-CBC but in OFF-CBC

  
   

  • Reduced protein levels (e.g. Cav1.4, CTBP2, ELFN1, mGlur6, TRPM1)

  
   

  • BC neurite sprouting

  
   

  • Ribbons in cone pedicles of α2δ-4-KO mice appear mostly normal in structure.

  
   

  • Ribbon structures in cones appeared unaffected.

  
   

  • Less than one-third of cone ribbons show the expected triadic organization of processes at ribbon sites.

  • Reduced photopic b-wave.

  
    In patients, α2δ-4 variants cause cone- rod dystrophy  
ELFN ELFN1-KO

  • ERG: Loss of scotopic transmission, while photopic transmission remains unaffected.

 [91,110]
  ELFN2-KO

  • Did not disrupt transmission from cones to ON-cone bipolar cells.

  
   

  • Exclusively localized in cone photoreceptors.

  
    However, a double knockout of both ELFN1 and ELFN2 completely prevented synaptic transmission in cones.