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Jacobus J. Dudok, Alicia Sanz Sanz, Ditte Lundvig, Eric C. Swindell, Milan Jamrich, Jan Wijnholds; Generation and Analysis of Mpp3 Conditional Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4347.
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© ARVO (1962-2015); The Authors (2016-present)
Membrane Palmitoylated Protein 3 (MPP3) is a member of the Membrane Associated Guanylate Kinase (MAGUK) family and is expressed in retina and brain. MPP3 and CRB1 interact directly with PALS1/MPP5 and may form a protein complex or mutual exclusive complexes since MPP3 does not bind CRB1. Additionally, MPP3 can interact with DLG1 and the 5-HT2C receptor. MPP3 might be implicated in regulating polarity, synaptogenesis and vesicle release. In the retina, MPP3 is localized at the subapical region adjacent to the outer limiting membrane (OLM) and in the outer plexiform layer. The aim of this study is to further unravel the role of MPP3 in retina and brain.
We have generated Mpp3 conditional knockout (cKO) mice. We have crossed Mpp3 cKO mice with Rx-Cre mice, to specifically abolish Mpp3 in the retina. To investigate the effect of deletion of MPP3 on retinal morphology and localization of other proteins in the retina, we performed immunohistochemical and morphological analysis on these retinas.
Analysis of retinas from eight week old Mpp3F/F RxCreTg/+ mice showed that there was a mild morphological phenotype. At foci, ectopic photoreceptor nuclei were detected in the subretinal space, suggesting that the integrity of the OLM might be compromised at these areas. Immunohistochemical analysis of these retinas revealed that levels and distribution of DLG1 was not affected in Mpp3F/F RxCreTg/+ mice. However, levels of PALS1 at the OLM seemed to be decreased in Mpp3F/F RxCreTg/+ mice compared to control. Immunohistochemical analysis of levels of CRB1, CRB2 and MUPP1 showed that these were not different between eight week old Mpp3F/F RxCreTg/+ and control mice.
These data suggest that MPP3 is dispensable for proper morphological development of the retina, but might be required for stabilizing PALS1. This suggests that MPP3 might function as a modulator of PALS1 and the Crumbs complex in the retina.
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