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J. Won, R.S. Smith, N.S. Peachey, J. Wu, W.L. Hicks, J.K. Naggert, P.M. Nishina; Expression and Localization of MFRP and C1QTNF5 in the Developing Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4201.
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© ARVO (1962-2015); The Authors (2016-present)
Mfrp (membrane–type frizzled–related protein) is mutated in retinal degeneration 6 (rd6) mice. Although a 4 base pair deletion in a splice donor site of Mfrp is known to lead to skipping of exon 4, little known about how the mutant protein causes the degenerative retinal phenotype observed. Here we examine the early pathological changes in the rd6 mouse model and determine the expression pattern of the dicistronic Mfrp/C1qtnf5 message and localization of the proteins during retinal development.
Pathological changes in rd6 mice were monitored by light and electron microscopy, immunohistochemistry, and electroretinography and compared to age–matched control mice from P0 to P28. mRNA levels and localization of MFRP and C1QTNF5 were determined by quantitative PCR (QPCR) and immunohistochemistry, respectively.
Outer segments in rd6 mice were disorganized and shorter than in WT controls at P14 but the outer nuclear layer thickness in mutant and controls was the same. mRNA expression assessed by QPCR of Mfrp and C1qtnf5 was highest at P14 in WT animals but at P28 in rd6 animals. Immunohistochemical analysis revealed that MFRP expression was restricted to the apical processes of RPE cells in WT controls but was not detectable in rd6 mice. The localization of C1QTNF5 was detected exclusively in the both apical and basal membrane of the RPE at P7 in both WT and rd6 mice. However, in adult mice, it was detected in the ELM and OPL as well as the RPE. Expression of Ezrin and Na+/K+ ATPase, which are present in the apical membrane of the RPE, was not affected in rd6 mice and blue and green/red opsins were also not affected. However, rhodopsin staining in rd6 mice was more diffuse than that observed in WT controls. At P25, the rod ERG a–wave of rd6 mice was reduced in amplitude by 50% as were ERG components generated by the RPE.
Rd6, an age–related retinal degeneration model shows early pathological changes prior to the loss of photoreceptors. MFRP was absent or not detected by our antibody in apical processes of the RPE cells of rd6 mice. Outer segment structure and rod photoreceptor function were abnormal prior to an actual loss of the PR cell bodies.
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