Deletion of connexin45 in mouse retinal neurons disrupts the rod/cone signaling pathway between AII amacrine and ON cone bipolar cells and leads to impaired visual transmission.
Connexin45 (Cx45) is known to be expressed in the retina, but its functional analysis was problematic because general deletion of Cx45 coding DNA resulted in cardiovascular defects and embryonic lethality at embryonic day 10.5. We generated mice with neuron-directed deletion of Cx45 and concomitant activation of the enhanced green fluorescent protein (EGFP). EGFP labeling was observed in bipolar, amacrine, and ganglion cell populations. Intracellular microinjection of fluorescent dyes in EGFP-labeled somata combined with immunohistological markers revealed Cx45 expression in both ON and OFF cone bipolar cells. The scotopic electroretinogram of mutant mice revealed a normal a-wave but a 40% reduction in the b-wave amplitude, similar to that found in Cx36-deficient animals, suggesting a possible defect in the rod pathway of visual transmission. Indeed, neurotransmitter coupling between AII amacrine cells and Cx45-expressing cone bipolar cells was disrupted in Cx45-deficient mice. These data suggest that both Cx45 and Cx36 participate in the formation of functional heterotypic electrical synapses between these two types of retinal neurons that make up the major rod pathway.
Maxeiner
Stephan
S
Institute for Genetics, Division of Molecular Genetics, University of Bonn, 53117 Bonn, Germany.
Dedek
Karin
K
Janssen-Bienhold
Ulrike
U
Ammermüller
Josef
J
Brune
Hendrik
H
Kirsch
Taryn
T
Pieper
Mario
M
Degen
Joachim
J
Krüger
Olaf
O
Willecke
Klaus
K
Weiler
Reto
R
D025042:Amacrine Cells / Q000502:physiology; D000818:Animals; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004596:Electroretinography; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D019426:Integrases; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D012160:Retina / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology*
D017630:Connexins; D005136:Eye Proteins; C082920:connexin 45; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases