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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

Published online by Cambridge University Press:  09 March 2006

BO CHANG
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine
JOHN R. HECKENLIVELY
Affiliation:
Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, California W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
PHILIPPA R. BAYLEY
Affiliation:
Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon
NICHOLAS C. BRECHA
Affiliation:
Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, California Departments of Neurobiology and Medicine, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California Research Service, VAGLAHS, Los Angeles, California
MURIEL T. DAVISSON
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine
NORM L. HAWES
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine
ARLENE A. HIRANO
Affiliation:
Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, California Departments of Neurobiology and Medicine, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California Research Service, VAGLAHS, Los Angeles, California
RONALD E. HURD
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine
AKIHIRO IKEDA
Affiliation:
Department of Genetics, University of Wisconsin, Madison, Wisconsin
BRITT A. JOHNSON
Affiliation:
Department of Genetics, University of Wisconsin, Madison, Wisconsin
MAUREEN A. MCCALL
Affiliation:
Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky The Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky
CATHERINE W. MORGANS
Affiliation:
Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon
STEVE NUSINOWITZ
Affiliation:
Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, California
NEAL S. PEACHEY
Affiliation:
Research Service, Cleveland VAMC, Cleveland, Ohio Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
DENNIS S. RICE
Affiliation:
Lexicon Genetics, The Woodlands, Texas
KIRSTAN A. VESSEY
Affiliation:
Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky
RONALD G. GREGG
Affiliation:
The Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, Kentucky

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.

Type
Research Article
Copyright
2006 Cambridge University Press

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