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Gene Review

Pde6b  -  phosphodiesterase 6B, cGMP, rod receptor,...

Mus musculus

Synonyms: GMP-PDE beta, Mpb, Pdeb, Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta, rd, ...
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Disease relevance of Pde6b

  • CONCLUSIONS: The slowing of degeneration in the rd/rd and Q344ter mutant mice demonstrated that intraocularly injected survival factors can protect photoreceptors from degenerating in animal models with the same or similar genetic defects as those in human inherited retinal degenerations [1].
  • The rd1 mouse is a relevant model for studying the mechanisms of photoreceptor degeneration in retinitis pigmentosa [2].
  • In the inherited degenerative retinal disease of the rd mouse, rod cGMP levels rise above normal due to depressed cGMP-phosphodiesterase (cGMP-PDE) function a few days before degeneration begins [3].
  • The provirus is present in every strain of rd mouse tested [4].
  • HIV vectors containing a gene encoding a hemagglutinin (HA)-tagged PDEbeta were injected into the subretinal spaces of newborn rd mouse eyes [5].

Psychiatry related information on Pde6b

  • Because rd gene induces different age-related degeneration of cones and rods, we have examined age-related changes in the sensitivity to a light pulse for phase-shifting the locomotor activity rhythms in CBA/J-rd/rd mice [6].

High impact information on Pde6b


Chemical compound and disease context of Pde6b


Biological context of Pde6b

  • RESULTS: Point mutations in the seven new alleles of Pde6b were identified: Three generated premature stop codons, two were missense mutations, and two were splice mutations [14].
  • Photoreceptor cell death in mice expressing one of the bcl transgenes and carrying either the rd mutation homozygously or the rhodopsin mutation heterozygously was examined by histologic and electroretinographic measurements [15].
  • Apoptosis-related nuclear DNA fragmentation, as assessed by in situ labeling with terminal deoxynucleotidyl transferase, was present in 13-day-old rd/rd mouse retinas with or without transgene expression [15].
  • We have utilized backcross analysis in mice to verify and define more precisely the location of the Pdeb locus 6.1 +/- 2.3 cM distal of Mgsa on mouse chromosome 5 [16].
  • Linkage of the mouse Pdeb locus with other homologues in the human 4p16.3 region is maintained but gene order is not, suggesting at least three possible sites for the corresponding mouse HD gene [16].

Anatomical context of Pde6b


Associations of Pde6b with chemical compounds

  • METHODS: Retinal morphometry was performed at the light microscopic level in caspase-3 mutant mice from PN0 through PN23, and in rd-1/caspase-3 double mutant mice at PN14, -16, and -18 [21].
  • To genetically define the roles of these pigments in light modulation of behavior, we generated rd/rd;mCry1(-)/mCry1(-);mCry2(-)/mCry2(-) mutant mice lacking rods and most cones as well as both cryptochrome proteins [20].
  • To examine this hypothesis further, a murine photoreceptor-derived cell line (661W) was treated with the Ca(2+) ionophore A23187, cGMP-gated channel agonist 8-bromo-cGMP, or phosphodiesterase inhibitor isobutylmethylxanthine to mimic the increased Ca(2+) influx seen in the rd photoreceptors [22].
  • It is suggested that in the rd mouse the absence of photoreceptors, perhaps coupled with lack of normal interphotoreceptor matrix, leads to a loss in the ability of the pigment epithelium to store retinyl esters [23].
  • Using microarray techniques, transcript levels of cyclic AMP response element-binding protein (CREB)-1, calpastatin and of various calpain genes were analysed in the rd1 mouse compared with its wild-type control [24].

Regulatory relationships of Pde6b


Other interactions of Pde6b

  • PURPOSE: The primary purpose of this study was to evaluate the impact of caspase-3 ablation on photoreceptor degeneration in the rd-1 mouse [21].
  • Since the rd gene is located on mouse chromosome 5, our results suggest that Sag is not the site of the rd mutation [28].
  • Genotyping confirmed the presence of a viral insertion of rd1 gene in the mocha strain [29].
  • Since the locus of the rd mutation is on mouse chromosome 5, a defect in the Pdea gene is ruled out as the cause of this inherited retinal degeneration [3].
  • In a recent study, we reported that bFGF content and mRNA expression levels are elevated in degenerating photoreceptors in the rd mouse retina as compared to the levels in photoreceptors in age matched normal retinas (Gao and Hollyfield, 1995) [30].

Analytical, diagnostic and therapeutic context of Pde6b


  1. Protection of mouse photoreceptors by survival factors in retinal degenerations. LaVail, M.M., Yasumura, D., Matthes, M.T., Lau-Villacorta, C., Unoki, K., Sung, C.H., Steinberg, R.H. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  2. CNTF+BDNF treatment and neuroprotective pathways in the rd1 mouse retina. Azadi, S., Johnson, L.E., Paquet-Durand, F., Perez, M.T., Zhang, Y., Ekström, P.A., van Veen, T. Brain Res. (2007) [Pubmed]
  3. Genetic mapping demonstrates that the alpha-subunit of retinal cGMP-phosphodiesterase is not the site of the rd mutation. Danciger, M., Kozak, C.A., Li, T., Applebury, M.L., Farber, D.B. Exp. Eye Res. (1990) [Pubmed]
  4. Localization of a retroviral element within the rd gene coding for the beta subunit of cGMP phosphodiesterase. Bowes, C., Li, T., Frankel, W.N., Danciger, M., Coffin, J.M., Applebury, M.L., Farber, D.B. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  5. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. Takahashi, M., Miyoshi, H., Verma, I.M., Gage, F.H. J. Virol. (1999) [Pubmed]
  6. Decline of circadian photosensitivity associated with retinal degeneration in CBA/J-rd/rd mice. Yoshimura, T., Ebihara, S. Brain Res. (1998) [Pubmed]
  7. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Bowes, C., Li, T., Danciger, M., Baxter, L.C., Applebury, M.L., Farber, D.B. Nature (1990) [Pubmed]
  8. Bone marrow-derived stem cells preserve cone vision in retinitis pigmentosa. Smith, L.E. J. Clin. Invest. (2004) [Pubmed]
  9. Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Chang, G.Q., Hao, Y., Wong, F. Neuron (1993) [Pubmed]
  10. Tool from ancient pharmacopoeia prevents vision loss. Boatright, J.H., Moring, A.G., McElroy, C., Phillips, M.J., Do, V.T., Chang, B., Hawes, N.L., Boyd, A.P., Sidney, S.S., Stewart, R.E., Minear, S.C., Chaudhury, R., Ciavatta, V.T., Rodrigues, C.M., Steer, C.J., Nickerson, J.M., Pardue, M.T. Mol. Vis. (2006) [Pubmed]
  11. Multidestructive pathways triggered in photoreceptor cell death of the rd mouse as determined through gene expression profiling. Rohrer, B., Pinto, F.R., Hulse, K.E., Lohr, H.R., Zhang, L., Almeida, J.S. J. Biol. Chem. (2004) [Pubmed]
  12. Characterization of a phosphodiesterase-immunoreactive polypeptide from rod photoreceptors of developing rd mouse retinas. Lee, R.H., Navon, S.E., Brown, B.M., Fung, B.K., Lolley, R.N. Invest. Ophthalmol. Vis. Sci. (1988) [Pubmed]
  13. Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration. Sanz, M.M., Johnson, L.E., Ahuja, S., Ekström, P.A., Romero, J., van Veen, T. Neuroscience (2007) [Pubmed]
  14. Genotype-phenotype correlation of mouse pde6b mutations. Hart, A.W., McKie, L., Morgan, J.E., Gautier, P., West, K., Jackson, I.J., Cross, S.H. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  15. Overexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration. Joseph, R.M., Li, T. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  16. Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3). Altherr, M.R., Wasmuth, J.J., Seldin, M.F., Nadeau, J.H., Baehr, W., Pittler, S.J. Genomics (1992) [Pubmed]
  17. Growth factors in combination, but not individually, rescue rd mouse photoreceptors in organ culture. Ogilvie, J.M., Speck, J.D., Lett, J.M. Exp. Neurol. (2000) [Pubmed]
  18. Light-induced c-fos in melanopsin retinal ganglion cells of young and aged rodless/coneless (rd/rd cl) mice. Semo, M., Lupi, D., Peirson, S.N., Butler, J.N., Foster, R.G. Eur. J. Neurosci. (2003) [Pubmed]
  19. Photoreceptor-specific protein expression of mouse retina in organ culture and retardation of rd degeneration in vitro by a combination of basic fibroblast and nerve growth factors. Caffé, A.R., Söderpalm, A., van Veen, T. Curr. Eye Res. (1993) [Pubmed]
  20. Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Selby, C.P., Thompson, C., Schmitz, T.M., Van Gelder, R.N., Sancar, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  21. Caspase-3 in postnatal retinal development and degeneration. Zeiss, C.J., Neal, J., Johnson, E.A. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  22. Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line. Sharma, A.K., Rohrer, B. J. Biol. Chem. (2004) [Pubmed]
  23. Rhodopsin, 11-cis vitamin A, and interstitial retinol-binding protein (IRBP) during retinal development in normal and rd mutant mice. Carter-Dawson, L., Alvarez, R.A., Fong, S.L., Liou, G.I., Sperling, H.G., Bridges, C.D. Dev. Biol. (1986) [Pubmed]
  24. Calpain is activated in degenerating photoreceptors in the rd1 mouse. Paquet-Durand, F., Azadi, S., Hauck, S.M., Ueffing, M., van Veen, T., Ekström, P. J. Neurochem. (2006) [Pubmed]
  25. Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Bennett, J., Zeng, Y., Bajwa, R., Klatt, L., Li, Y., Maguire, A.M. Gene Ther. (1998) [Pubmed]
  26. Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Frasson, M., Picaud, S., Léveillard, T., Simonutti, M., Mohand-Said, S., Dreyfus, H., Hicks, D., Sabel, J. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
  27. Spatio-temporal analysis of light-induced Fos expression in the retina of rd mutant mice. Huerta, J.J., Llamosas, M.M., Cernuda-Cernuda, R., García-Fernández, J.M. Brain Res. (1999) [Pubmed]
  28. The gene for retinal S-antigen (48-kDa protein) maps to the centromeric portion of mouse chromosome 1 near Idh-1. Danciger, M., Kozak, C.A., Tsuda, M., Shinohara, T., Farber, D.B. Genomics (1989) [Pubmed]
  29. Photoreceptor degeneration and rd1 mutation in the grizzled/mocha mouse strain. Qiao, X., Pennesi, M., Seong, E., Gao, H., Burmeister, M., Wu, S.M. Vision Res. (2003) [Pubmed]
  30. Basic fibroblast growth factor: increased gene expression in inherited and light-induced photoreceptor degeneration. Gao, H., Hollyfield, J.G. Exp. Eye Res. (1996) [Pubmed]
  31. NIH Swiss and Black Swiss mice have retinal degeneration and performance deficits in cognitive tests. Clapcote, S.J., Lazar, N.L., Bechard, A.R., Wood, G.A., Roder, J.C. Comp. Med. (2005) [Pubmed]
  32. Isolation of a candidate cDNA for the gene causing retinal degeneration in the rd mouse. Bowes, C., Danciger, M., Kozak, C.A., Farber, D.B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
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