Human Molecular Genetics, 2002, Vol. 11, No. 16 1879-1886
© 2002 Oxford University Press
Mfrp, a gene encoding a frizzled related protein, is mutated in the mouse retinal degeneration 6
1The Jackson Laboratory, Bar Harbor, ME 04609, USA, 2Department of Ophthalmology, Akita University School of Medicine, Akita 010-8543, Japan and 3Jules Stein Eye Institute/UCLA, Los Angeles, CA 90095, USA
Received April 19, 2002; Revised June 3, 2002; Accepted June 4, 2002
The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolog of the human membrane-type frizzled-related protein (Mfrp) gene that results in the skipping of exon 4. We found that mRNA of Mfrp is predominantly expressed in the eye, and at a lower level in the brain. To determine where in the eye Mfrp is expressed, in situ hybridization was done and showed that Mfrp is expressed specifically in the retinal pigment epithelium (RPE) and ciliary epithelium of the eye. The deduced amino acid sequence of MFRP contains a region with similarities to the cysteine-rich domain (CRD) of frizzled, a gene originally found in Drosophila that controls tissue polarity. The CRD is essential for Wnt binding and signaling. Wnt signaling has been shown to be involved in the control of gene expression, cell adhesion, planar polarity, proliferation and apoptosis. We also observed the localization of Wnt family proteins in the apical membrane of the RPE. Our results provide genetic evidence for an involvement of the Mfrp gene expressed by RPE in the degeneration of photoreceptors.
* To whom correspondence should be addressed. Tel: +1 2072886383; Fax: +1 2072886077; Email: pmn{at}aretha.jax.org
AF469650 (cDNA sequence of Mfrp and C1qtnf5).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Yi, R. E. I. Nakamura, O. Mohamed, D. Dufort, and A. S. Hackam Characterization of Wnt Signaling during Photoreceptor Degeneration Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5733 - 5741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. A. Mandal, V. Vasireddy, G. B. Reddy, X. Wang, S. E. Moroi, B. R. Pattnaik, B. A. Hughes, J. R. Heckenlively, P. F. Hitchcock, M. M. Jablonski, et al. CTRP5 Is a Membrane-Associated and Secretory Protein in the RPE and Ciliary Body and the S163R Mutation of CTRP5 Impairs Its Secretion Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5505 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. A. Mandal, V. Vasireddy, M. M. Jablonski, X. Wang, J. R. Heckenlively, B. A. Hughes, G. B. Reddy, and R. Ayyagari Spatial and Temporal Expression of MFRP and Its Interaction with CTRP5 Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5514 - 5521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shu, B. Tulloch, A. Lennon, D. Vlachantoni, X. Zhou, C. Hayward, and A. F. Wright Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5 Hum. Mol. Genet., May 15, 2006; 15(10): 1680 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ayyagari, M. N. A. Mandal, A. J. Karoukis, L. Chen, N. C. McLaren, M. Lichter, D. T. Wong, P. F. Hitchcock, R. C. Caruso, S. E. Moroi, et al. Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3363 - 3371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. H. Sundin, G. S. Leppert, E. D. Silva, J.-M. Yang, S. Dharmaraj, I. H. Maumenee, L. C. Santos, C. F. Parsa, E. I. Traboulsi, K. W. Broman, et al. Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein PNAS, July 5, 2005; 102(27): 9553 - 9558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Seiler, K. C. Finger-Baier, O. Rinner, Y. V. Makhankov, H. Schwarz, S. C. F. Neuhauss, and T. Nicolson Duplicated genes with split functions: independent roles of protocadherin15 orthologues in zebrafish hearing and vision Development, February 1, 2005; 132(3): 615 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yu, S. He, J. S. Friedman, M. Akimoto, D. Ghosh, A. J. Mears, D. Hicks, and A. Swaroop Altered Expression of Genes of the Bmp/Smad and Wnt/Calcium Signaling Pathways in the Cone-only Nrl-/- Mouse Retina, Revealed by Gene Profiling Using Custom cDNA Microarrays J. Biol. Chem., October 1, 2004; 279(40): 42211 - 42220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lord-Grignon, N. Tetreault, A. J. Mears, A. Swaroop, and G. Bernier Characterization of New Transcripts Enriched in the Mouse Retina and Identification of Candidate Retinal Disease Genes Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3313 - 3319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hayward, X. Shu, A. V. Cideciyan, A. Lennon, P. Barran, S. Zareparsi, L. Sawyer, G. Hendry, B. Dhillon, A. H. Milam, et al. Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration Hum. Mol. Genet., October 16, 2003; 12(20): 2657 - 2667. [Abstract] [Full Text] [PDF]
|
|