Abstract
We have previously demonstrated that there is a low level of transcription of tissue-specific genes in every cell type. In this study, we have taken advantage of this phenomenon, called illegitimate transcription, to analyze the muscle-type dystrophin mRNA in easily accessible cells such as lymphoid cells, fibroblasts, and peripheral blood cells from Duchenne and Becker muscular dystrophies with known internal gene deletion. The results showed that, in the studied regions surrounding the deletions, processing of truncated transcripts is identical in specific (muscle tissue) and in nonspecific cells (lymphoid cells). In Becker cases with out-of-frame deletions, the already described alternatively spliced species found in muscle samples were also found in nonspecific cells. These results demonstrate that illegitimate transcripts are a bona fide version of tissue-specific mRNA, and that they represent a useful material to investigate the qualitative consequences of gene defects at the mRNA level.
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- Berg L. P., Wieland K., Millar D. S., Schlösser M., Wagner M., Kakkar V. V., Reiss J., Cooper D. N. Detection of a novel point mutation causing haemophilia A by PCR/direct sequencing of ectopically-transcribed factor VIII mRNA. Hum Genet. 1990 Oct;85(6):655–658. doi: 10.1007/BF00193593. [DOI] [PubMed] [Google Scholar]
- Chelly J., Concordet J. P., Kaplan J. C., Kahn A. Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2617–2621. doi: 10.1073/pnas.86.8.2617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chelly J., Gilgenkrantz H., Lambert M., Hamard G., Chafey P., Récan D., Katz P., de la Chapelle A., Koenig M., Ginjaar I. B. Effect of dystrophin gene deletions on mRNA levels and processing in Duchenne and Becker muscular dystrophies. Cell. 1990 Dec 21;63(6):1239–1248. doi: 10.1016/0092-8674(90)90419-f. [DOI] [PubMed] [Google Scholar]
- Chelly J., Kaplan J. C., Maire P., Gautron S., Kahn A. Transcription of the dystrophin gene in human muscle and non-muscle tissue. Nature. 1988 Jun 30;333(6176):858–860. doi: 10.1038/333858a0. [DOI] [PubMed] [Google Scholar]
- Chelly J., Marlhens F., Dutrillaux B., Van Ommen G. J., Lambert M., Haioun B., Boissinot G., Fardeau M., Kaplan J. C. Deletion proximal to DXS68 locus (L1 probe site) in a boy with Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal hypoplasia. Hum Genet. 1988 Mar;78(3):222–227. doi: 10.1007/BF00291665. [DOI] [PubMed] [Google Scholar]
- Chelly J., Montarras D., Pinset C., Berwald-Netter Y., Kaplan J. C., Kahn A. Quantitative estimation of minor mRNAs by cDNA-polymerase chain reaction. Application to dystrophin mRNA in cultured myogenic and brain cells. Eur J Biochem. 1990 Feb 14;187(3):691–698. doi: 10.1111/j.1432-1033.1990.tb15355.x. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Gilgenkrantz H., Chelly J., Lambert M., Récan D., Barbot J. C., van Ommen G. J., Kaplan J. C. Analysis of molecular deletions with cDNA probes in patients with Duchenne and Becker muscular dystrophies. Genomics. 1989 Oct;5(3):574–580. doi: 10.1016/0888-7543(89)90025-6. [DOI] [PubMed] [Google Scholar]
- Hoffman E. P., Fischbeck K. H., Brown R. H., Johnson M., Medori R., Loike J. D., Harris J. B., Waterston R., Brooke M., Specht L. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med. 1988 May 26;318(21):1363–1368. doi: 10.1056/NEJM198805263182104. [DOI] [PubMed] [Google Scholar]
- Knebelmann B., Boussin L., Guerrier D., Legeai L., Kahn A., Josso N., Picard J. Y. Anti-Müllerian hormone Bruxelles: a nonsense mutation associated with the persistent Müllerian duct syndrome. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3767–3771. doi: 10.1073/pnas.88.9.3767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koenig M., Beggs A. H., Moyer M., Scherpf S., Heindrich K., Bettecken T., Meng G., Müller C. R., Lindlöf M., Kaariainen H. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet. 1989 Oct;45(4):498–506. [PMC free article] [PubMed] [Google Scholar]
- Koenig M., Hoffman E. P., Bertelson C. J., Monaco A. P., Feener C., Kunkel L. M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509–517. doi: 10.1016/0092-8674(87)90504-6. [DOI] [PubMed] [Google Scholar]
- Koenig M., Monaco A. P., Kunkel L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219–228. doi: 10.1016/0092-8674(88)90383-2. [DOI] [PubMed] [Google Scholar]
- Lindlöf M., Kiuru A., Käriäinen H., Kalimo H., Lang H., Pihko H., Rapola J., Somer H., Somer M., Savontaus M. L. Gene deletions in X-linked muscular dystrophy. Am J Hum Genet. 1989 Apr;44(4):496–503. [PMC free article] [PubMed] [Google Scholar]
- Malhotra S. B., Hart K. A., Klamut H. J., Thomas N. S., Bodrug S. E., Burghes A. H., Bobrow M., Harper P. S., Thompson M. W., Ray P. N. Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science. 1988 Nov 4;242(4879):755–759. doi: 10.1126/science.3055295. [DOI] [PubMed] [Google Scholar]
- Monaco A. P., Bertelson C. J., Liechti-Gallati S., Moser H., Kunkel L. M. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics. 1988 Jan;2(1):90–95. doi: 10.1016/0888-7543(88)90113-9. [DOI] [PubMed] [Google Scholar]
- Roberts R. G., Bentley D. R., Barby T. F., Manners E., Bobrow M. Direct diagnosis of carriers of Duchenne and Becker muscular dystrophy by amplification of lymphocyte RNA. Lancet. 1990 Dec 22;336(8730):1523–1526. doi: 10.1016/0140-6736(90)93305-9. [DOI] [PubMed] [Google Scholar]
- Sarkar G., Sommer S. S. Access to a messenger RNA sequence or its protein product is not limited by tissue or species specificity. Science. 1989 Apr 21;244(4902):331–334. doi: 10.1126/science.2565599. [DOI] [PubMed] [Google Scholar]
- Schloesser M., Slomski R., Wagner M., Reiss J., Berg L. P., Kakkar V. V., Cooper D. N. Characterization of pathological dystrophin transcripts from the lymphocytes of a muscular dystrophy carrier. Mol Biol Med. 1990 Dec;7(6):519–523. [PubMed] [Google Scholar]