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(Investigative Ophthalmology and Visual Science. 2005;46:4320-4327.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0478
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A Critical Role of CaBP4 in the Cone Synapse

Tadao Maeda,1 Janis Lem,2 Krzysztof Palczewski,1,3,4 and Françoise Haeseleer1

1From the Departments of Ophthalmology, 3Pharmacology, and 4Chemistry, University of Washington, Seattle, Washington; and the 2Departments of Ophthalmology and Molecular Cardiology, Tufts–New England Med Center, Boston, Massachusetts.

PURPOSE. CaBP4, a photoreceptor-specific protein of the rods and cones, is essential for the development and maintenance of the mouse photoreceptor synapse. In this study, double CaBP4/rod {alpha}-transducin knockout (Cabp4–/–Gnat1–/–) mice lacking the rod-mediated component of electrophysiologic responses were generated and analyzed to investigate the role of CaBP4 in cones.

METHODS. The retinal morphology and physiologic function of 2-month-old Cabp4–/–Gnat1–/– mice were analyzed using immunocytochemistry, electron microscopy, and single-flash and flicker electroretinography (ERG).

RESULTS. The thickness of the outer plexiform layer and the number of photoreceptor terminals in Cabp4–/–Gnat1–/– mice were reduced to levels similar to those of Cabp4–/– mice. Single-flash and flicker ERG showed that the amplitude and sensitivity of the b-wave in the Cabp4–/–Gnat1–/– mice were severely attenuated compared with those in wild-type and Gnat1–/– mice.

CONCLUSIONS. Results indicate that the cone synaptic function in Cabp4–/–Gnat1–/– mice was severely disrupted, whereas the morphologic defects observed in Cabp4–/–Gnat1–/– mice were similar to those of single Cabp4–/– knockout mice. This and a previous study reveal that CaBP4 is critical for signal transmission from rods and cones to second-order neurons.




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