TY - JOUR
T1 - Phospholipase β4-knockout mouse exhibits retinal phenotype
AU - Jiang, Huiping
AU - Lyubarsky, A.
AU - Vardi, N.
AU - Pugh Jr, Edward N
AU - Chen, J.
AU - Xu, J.
AU - Simon, M. I.
AU - Wu, Dianqing
PY - 1996/2/15
Y1 - 1996/2/15
N2 - Purpose: Determine if PLC-β4 has a retinal function by making/assessing a mouse knockout. Rationale: PLC-β4 is one of the four PLC-β isoforms that have been cloned and can be activated by the Gα subunits of G-proteins of the Gq class, but not by the Gβγ subunits. PLC-β4 shares a closer homology to the NorpA protein (which mediates phototransduction in Drosopnila) than to the isoforms PLC-β1-β3. Previous immunohistochemical studies have shown that PLC-β4 is expressed in cone photoreceptors, and in bipolar and ganglion cells1. Method: A mouse line was generated in which the PLC-β4 genes are disrupted. Retinal rod function was assessed with single-flash a- and b-wave electroretinography. Anatomical analysis of rod density, rod outer segment length and other basic parameters is underway. Results: Extracts of retinal and brain tissues of two animals from each genotype (+/+, +/-, -/-) were examined. Western analysis with a PLC-β4 - specific antibody found no detectable PLC-β4 protein in -/- animals. ERGs of three -/- mice age12-15 weeks showed a-wave maximum amplitudes (amax reduced about 7-8 fold from controls (amax = 460 ± 140 μV), though a-wave sensitivity to light was approximately normal. Both rod and cone b-wave components were severely diminished in amplitude. Preleminary examination of the retinas of the animals whose ERGs were recorded suggests some retinal deterioration has occurred in these animals. Conclusion: The preliminary results demonstrate a requirement for PLC-β4 in normal retinal function. Developmental, anatomical and functional analysis now underway may help to determine the specific role of PLC-β4.
AB - Purpose: Determine if PLC-β4 has a retinal function by making/assessing a mouse knockout. Rationale: PLC-β4 is one of the four PLC-β isoforms that have been cloned and can be activated by the Gα subunits of G-proteins of the Gq class, but not by the Gβγ subunits. PLC-β4 shares a closer homology to the NorpA protein (which mediates phototransduction in Drosopnila) than to the isoforms PLC-β1-β3. Previous immunohistochemical studies have shown that PLC-β4 is expressed in cone photoreceptors, and in bipolar and ganglion cells1. Method: A mouse line was generated in which the PLC-β4 genes are disrupted. Retinal rod function was assessed with single-flash a- and b-wave electroretinography. Anatomical analysis of rod density, rod outer segment length and other basic parameters is underway. Results: Extracts of retinal and brain tissues of two animals from each genotype (+/+, +/-, -/-) were examined. Western analysis with a PLC-β4 - specific antibody found no detectable PLC-β4 protein in -/- animals. ERGs of three -/- mice age12-15 weeks showed a-wave maximum amplitudes (amax reduced about 7-8 fold from controls (amax = 460 ± 140 μV), though a-wave sensitivity to light was approximately normal. Both rod and cone b-wave components were severely diminished in amplitude. Preleminary examination of the retinas of the animals whose ERGs were recorded suggests some retinal deterioration has occurred in these animals. Conclusion: The preliminary results demonstrate a requirement for PLC-β4 in normal retinal function. Developmental, anatomical and functional analysis now underway may help to determine the specific role of PLC-β4.
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M3 - Article
AN - SCOPUS:0005022552
VL - 37
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 3
ER -