Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Oct 15;90(20):9616–9619. doi: 10.1073/pnas.90.20.9616

PCR analysis of DNA from 70-year-old sections of rodless retina demonstrates identity with the mouse rd defect.

S J Pittler 1, C E Keeler 1, R L Sidman 1, W Baehr 1
PMCID: PMC47620  PMID: 8415750

Abstract

Rodless retina (gene symbol, r) was discovered in mice by Keeler 70 years ago and was first described in this journal as an autosomal recessive mutation leading to "the absence of the visual cells (rods), the external nuclear layer, and the external molecular layer" [Keeler, C. E. (1924) Proc. Natl. Acad. Sci. USA 10, 329-333]. The mutation was studied by Keeler and others in the United States and Europe over the next decade, but Keeler's stock was destroyed in 1939, and mice definitively related to his by pedigree and progeny tests also appeared to have been lost by the end of World War II. In the early 1950s Brückner in Basel recognized mice with a similar retinal phenotype. Investigators in London and Strasbourg analyzed descendants of Brückner's mice and concluded, on the basis of different pathogenesis from r, that they carried a new mutation, which came later to be called retinal degeneration, rd. The relationship of r and rd has been unsettled ever since. Now that the rd phenotype is known to be due to a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene, we hoped to settle the question by direct analysis of r DNA. DNA was liberated from 70-year-old histological sections of +/r and r/r eyes, the only extant r DNA, and the regions encompassing the nonsense mutation amplified by the polymerase chain reaction (PCR). Sequence analysis of the PCR products revealed the presence of the same nonsense mutation and two intron polymorphisms in r DNA. PCR and direct sequence analysis of 11 strains of mice known to carry rd (or a similar allele) also revealed the presence of the nonsense mutation and the same intron polymorphisms. The fact that all r and rd mice contain an identical defect and intron polymorphisms in the phosphodiesterase beta-subunit gene settles beyond reasonable doubt that a single mutation arising > 70 years ago is now widely distributed through inbred mouse strains. Because of the extensive use of the name in publications of the past 40 years, we propose that the gene continue to be designated retinal degeneration, rd.

Full text

PDF
9616

Images in this article

9617Fig. 1
on p.9617
9618Fig. 3
on p.9618

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altherr M. R., Wasmuth J. J., Seldin M. F., Nadeau J. H., Baehr W., Pittler S. J. Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3). Genomics. 1992 Apr;12(4):750–754. doi: 10.1016/0888-7543(92)90305-c. [DOI] [PubMed] [Google Scholar]
  2. BRUCKNER R. Spaltlampenmikroskopie und Ophthalmoskopie am Auge von Ratte und Maus. Doc Ophthalmol. 1951;5-6:452–554. doi: 10.1007/BF00143667. [DOI] [PubMed] [Google Scholar]
  3. Carter-Dawson L. D., LaVail M. M., Sidman R. L. Differential effect of the rd mutation on rods and cones in the mouse retina. Invest Ophthalmol Vis Sci. 1978 Jun;17(6):489–498. [PubMed] [Google Scholar]
  4. Chang B., Heckenlively J. R., Hawes N. L., Roderick T. H. New mouse primary retinal degeneration (rd-3). Genomics. 1993 Apr;16(1):45–49. doi: 10.1006/geno.1993.1138. [DOI] [PubMed] [Google Scholar]
  5. Connell G., Bascom R., Molday L., Reid D., McInnes R. R., Molday R. S. Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):723–726. doi: 10.1073/pnas.88.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DIPAOLO J. A., NOELL W. K. Some genetic aspects of visual cell degeneration in mice. Exp Eye Res. 1962 Mar;1:215–220. doi: 10.1016/s0014-4835(62)80004-9. [DOI] [PubMed] [Google Scholar]
  7. DUNN T. B., ANDERVONT H. B. HISTOLOGY OF SOME NEOPLASMS AND NON-NEOPLASTIC LESIONS FOUND IN WILD MICE MAINTAINED UNDER LABORATORY CONDITIONS. J Natl Cancer Inst. 1963 Oct;31:873–901. [PubMed] [Google Scholar]
  8. Danciger M., Bowes C., Kozak C. A., LaVail M. M., Farber D. B. Fine mapping of a putative rd cDNA and its co-segregation with rd expression. Invest Ophthalmol Vis Sci. 1990 Aug;31(8):1427–1432. [PubMed] [Google Scholar]
  9. Farber D. B., Lolley R. N. Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina. Science. 1974 Nov 1;186(4162):449–451. doi: 10.1126/science.186.4162.449. [DOI] [PubMed] [Google Scholar]
  10. Farber D. B., Lolley R. N. Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina. J Cyclic Nucleotide Res. 1976;2(3):139–148. [PubMed] [Google Scholar]
  11. Gallagher D. S., Jr, Womack J. E., Baehr W., Pittler S. J. Syntenic assignments of visual transduction genes in cattle. Genomics. 1992 Nov;14(3):699–706. doi: 10.1016/s0888-7543(05)80171-5. [DOI] [PubMed] [Google Scholar]
  12. Holbach L. M., Font R. L., Baehr W., Pittler S. J. HSV antigens and HSV DNA in avascular and vascularized lesions of human herpes simplex keratitis. Curr Eye Res. 1991;10 (Suppl):63–68. doi: 10.3109/02713689109020359. [DOI] [PubMed] [Google Scholar]
  13. KARLI P. Contribution expérimentale à l'étude de la pathogénie des rétinoses pigmentaires. Ophthalmologica. 1954 Sep;128(3):137–162. doi: 10.1159/000302379. [DOI] [PubMed] [Google Scholar]
  14. KARLI P. Retines sans cellules visuelles; recherches morphologiques, physiologiques et physiopathologiques chez les rongeurs. Arch Anat Histol Embryol. 1952;35(1-2):1–76. [PubMed] [Google Scholar]
  15. Keeler C. E. On the Occurrence in the House Mouse of Mendelizing Structural Defect of the Retina Producing Blindness. Proc Natl Acad Sci U S A. 1926 Apr;12(4):255–258. doi: 10.1073/pnas.12.4.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Keeler C. E. Reoccurrence of four-row rodless mice. Arch Ophthalmol. 1970 Oct;84(4):499–504. doi: 10.1001/archopht.1970.00990040501020. [DOI] [PubMed] [Google Scholar]
  17. Keeler C. E., Sutcliffe E., Chaffee E. L. Normal and "Rodless" Retinae of the House Mouse with Respect to the Electromotive Force Generated through Stimulation by Light. Proc Natl Acad Sci U S A. 1928 Jun;14(6):477–484. doi: 10.1073/pnas.14.6.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Keeler C. E. The Inheritance of a Retinal Abnormality in White Mice. Proc Natl Acad Sci U S A. 1924 Jul;10(7):329–333. doi: 10.1073/pnas.10.7.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keeler C. Retinal degeneration in the mouse is rodless retina. J Hered. 1966 Mar-Apr;57(2):47–50. doi: 10.1093/oxfordjournals.jhered.a107462. [DOI] [PubMed] [Google Scholar]
  20. Lolley R. N., Schmidt S. Y., Farber D. B. Alterations in cyclic AMP metabolism associated with photoreceptor cell degeneration in the C3H mouse. J Neurochem. 1974 May;22(5):701–707. doi: 10.1111/j.1471-4159.1974.tb04283.x. [DOI] [PubMed] [Google Scholar]
  21. McLaughlin M. E., Sandberg M. A., Berson E. L., Dryja T. P. Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet. 1993 Jun;4(2):130–134. doi: 10.1038/ng0693-130. [DOI] [PubMed] [Google Scholar]
  22. NOELL W. K. Differentiation, metabolic organization, and viability of the visual cell. AMA Arch Ophthalmol. 1958 Oct;60(4 Pt 2):702–733. doi: 10.1001/archopht.1958.00940080722016. [DOI] [PubMed] [Google Scholar]
  23. PAIGEN K., NOELL W. K. Two linked genes showing a similar timing of expression in mice. Nature. 1961 Apr 8;190:148–150. doi: 10.1038/190148a0. [DOI] [PubMed] [Google Scholar]
  24. Pittler S. J., Baehr W. Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8322–8326. doi: 10.1073/pnas.88.19.8322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. SIDMAN R. L., GREEN M. C. RETINAL DEGENERATION IN THE MOUSE: LOCATION OF THE RD LOCUS IN LINKAGE GROUP XVII. J Hered. 1965 Jan-Feb;56:23–29. doi: 10.1093/oxfordjournals.jhered.a107364. [DOI] [PubMed] [Google Scholar]
  26. Schmidt S. Y., Lolley R. N. Cyclic-nucleotide phosphodiesterase: an early defect in inherited retinal degeneration of C3H mice. J Cell Biol. 1973 Apr;57(1):117–123. doi: 10.1083/jcb.57.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Suber M. L., Pittler S. J., Qin N., Wright G. C., Holcombe V., Lee R. H., Craft C. M., Lolley R. N., Baehr W., Hurwitz R. L. Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3968–3972. doi: 10.1073/pnas.90.9.3968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TANSLEY K. Hereditary degeneration of the mouse retina. Br J Ophthalmol. 1951 Oct;35(10):573–582. doi: 10.1136/bjo.35.10.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. THEILER K., CAGIANUT B. ZUR ERBLICHEN NETZHAUTDEGENERATION DER MAUS. Albrecht Von Graefes Arch Ophthalmol. 1963 Nov 28;166:387–396. [PubMed] [Google Scholar]
  30. Wimer R. E., Wimer C. C., Alameddine L., Cohen A. J. The mouse gene retinal degeneration (rd) may reduce the number of neurons present in the adult hippocampal dentate gyrus. Brain Res. 1991 May 3;547(2):275–278. doi: 10.1016/0006-8993(91)90971-w. [DOI] [PubMed] [Google Scholar]
  31. van Nie R., Iványi D., Démant P. A new H-2-linked mutation, rds, causing retinal degeneration in the mouse. Tissue Antigens. 1978 Aug;12(2):106–108. doi: 10.1111/j.1399-0039.1978.tb01305.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES