Abstract
To assess whether calcitonin is important in maintaining the integrity of bone the calcitonin gene of a young male patient with osteoporosis and no detectable plasma concentrations of calcitonin was studied. Genomic Southern blots with various restriction enzymes showed no large abnormalities in his calcitonin gene. Genomic clones representing his calcitonin gene were then analysed. His gene encoded normal precursor polypeptides for calcitonin and calcitonin gene related peptide; the only abnormality identified was a single base insertion in the intron separating exons IV and V of the gene. The affected sequence is homologous with an intron sequence from beta globin that is implicated in splicing and forming a crucial intermediate structure during the maturation of messenger RNA. The change observed may be responsible for the patient's calcitonin deficiency and consequently for his condition, suggesting that calcitonin is important in preventing bone loss.
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- Alevizaki M., Shiraishi A., Rassool F. V., Ferrier G. J., MacIntyre I., Legon S. The calcitonin-like sequence of the beta CGRP gene. FEBS Lett. 1986 Sep 29;206(1):47–52. doi: 10.1016/0014-5793(86)81338-2. [DOI] [PubMed] [Google Scholar]
- Bovenberg R. A., van de Meerendonk W. P., Baas P. D., Steenbergh P. H., Lips C. J., Jansz H. S. Model for alternative RNA processing in human calcitonin gene expression. Nucleic Acids Res. 1986 Nov 25;14(22):8785–8803. doi: 10.1093/nar/14.22.8785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Craig R. K., Hall L., Edbrooke M. R., Allison J., MacIntyre I. Partial nucleotide sequence of human calcitonin precursor mRNA identifies flanking cryptic peptides. Nature. 1982 Jan 28;295(5847):345–347. doi: 10.1038/295345a0. [DOI] [PubMed] [Google Scholar]
- Edbrooke M. R., Parker D., McVey J. H., Riley J. H., Sorenson G. D., Pettengill O. S., Craig R. K. Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma. EMBO J. 1985 Mar;4(3):715–724. doi: 10.1002/j.1460-2075.1985.tb03688.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Foroni L., Foldi J., Matutes E., Catovsky D., O'Connor N. J., Baer R., Forster A., Rabbitts T. H., Luzzatto L. Alpha, beta and gamma T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias. Br J Haematol. 1987 Nov;67(3):307–318. doi: 10.1111/j.1365-2141.1987.tb02352.x. [DOI] [PubMed] [Google Scholar]
- Hurley D. L., Tiegs R. D., Wahner H. W., Heath H., 3rd Axial and appendicular bone mineral density in patients with long-term deficiency or excess of calcitonin. N Engl J Med. 1987 Aug 27;317(9):537–541. doi: 10.1056/NEJM198708273170904. [DOI] [PubMed] [Google Scholar]
- Jonas V., Lin C. R., Kawashima E., Semon D., Swanson L. W., Mermod J. J., Evans R. M., Rosenfeld M. G. Alternative RNA processing events in human calcitonin/calcitonin gene-related peptide gene expression. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1994–1998. doi: 10.1073/pnas.82.7.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konarska M. M., Grabowski P. J., Padgett R. A., Sharp P. A. Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors. Nature. 1985 Feb 14;313(6003):552–557. doi: 10.1038/313552a0. [DOI] [PubMed] [Google Scholar]
- Leff S. E., Evans R. M., Rosenfeld M. G. Splice commitment dictates neuron-specific alternative RNA processing in calcitonin/CGRP gene expression. Cell. 1987 Feb 13;48(3):517–524. doi: 10.1016/0092-8674(87)90202-9. [DOI] [PubMed] [Google Scholar]
- McDermott M. T., Kidd G. S., Blue P., Ghaed V., Hofeldt F. D. Reduced bone mineral content in totally thyroidectomized patients: possible effect of calcitonin deficiency. J Clin Endocrinol Metab. 1983 May;56(5):936–939. doi: 10.1210/jcem-56-5-936. [DOI] [PubMed] [Google Scholar]
- Ruskin B., Green M. R. Specific and stable intron-factor interactions are established early during in vitro pre-mRNA splicing. Cell. 1985 Nov;43(1):131–142. doi: 10.1016/0092-8674(85)90018-2. [DOI] [PubMed] [Google Scholar]
- Stevenson J. C., White M. C., Joplin G. F., MacIntyre I. Osteoporosis and calcitonin deficiency. Br Med J (Clin Res Ed) 1982 Oct 9;285(6347):1010–1011. doi: 10.1136/bmj.285.6347.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]