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The nob2 mouse, a null mutation in Cacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

  • BO CHANG (a1), JOHN R. HECKENLIVELY (a2) (a3), PHILIPPA R. BAYLEY (a4), NICHOLAS C. BRECHA (a2) (a5) (a6), MURIEL T. DAVISSON (a1), NORM L. HAWES (a1), ARLENE A. HIRANO (a2) (a5) (a6), RONALD E. HURD (a1), AKIHIRO IKEDA (a7), BRITT A. JOHNSON (a7), MAUREEN A. MCCALL (a8) (a9), CATHERINE W. MORGANS (a4), STEVE NUSINOWITZ (a2), NEAL S. PEACHEY (a10) (a11), DENNIS S. RICE (a12), KIRSTAN A. VESSEY (a8) and RONALD G. GREGG (a9) (a13)...

Abstract

Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in the Cacna1f gene, encoding the α1F subunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in the nob2 (no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation in Cacna1f. Not surprisingly, the b-waves of both the light- and dark-adapted electroretinogram are abnormal in nob2 mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cells in vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate that nob2 mice are a valuable model in which to explore the pathophysiological mechanisms associated with Cacna1f mutations causing CSNB2, and the subsequent effects on visual information processing. Further, the nob2 mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.

Copyright

Corresponding author

Address correspondence and reprint requests to: Neal S. Peachey, Cole Eye Institute (I-31), Cleveland Clinic Foundation, Cleveland, OH 44106, USA. E-mail: peachen@ccf.org

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Keywords

The nob2 mouse, a null mutation in Cacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

  • BO CHANG (a1), JOHN R. HECKENLIVELY (a2) (a3), PHILIPPA R. BAYLEY (a4), NICHOLAS C. BRECHA (a2) (a5) (a6), MURIEL T. DAVISSON (a1), NORM L. HAWES (a1), ARLENE A. HIRANO (a2) (a5) (a6), RONALD E. HURD (a1), AKIHIRO IKEDA (a7), BRITT A. JOHNSON (a7), MAUREEN A. MCCALL (a8) (a9), CATHERINE W. MORGANS (a4), STEVE NUSINOWITZ (a2), NEAL S. PEACHEY (a10) (a11), DENNIS S. RICE (a12), KIRSTAN A. VESSEY (a8) and RONALD G. GREGG (a9) (a13)...

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