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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
. 1987 Mar;84(5):1454–1458. doi: 10.1073/pnas.84.5.1454

Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse.

L D Hudson, J A Berndt, C Puckett, C A Kozak, R A Lazzarini
PMCID: PMC304449  PMID: 3469678

Abstract

cDNA clones encoding proteolipid protein (PLP) were isolated from a mouse brain library and sequenced. We describe two transcripts arising from the PLP locus by alternative splicing: the major one encodes the 277-amino acid PLP protein and the minor one corresponds to the DM-20 protein, a PLP-like protein of 20,000 Mr that shares both amino and carboxyl regions with PLP. These two transcripts lack approximately 70 bases in PLP mRNA from the dysmyelinating jimpy mutant. The deletion spans amino acids 208-232; however, this region is present in the jimpy PLP-encoding gene. We propose that the jimpy mutant suffers a point mutation or the deletion of a few bases in the PLP gene that alters the normal splicing pattern and generates partially deleted PLP transcripts.

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Selected References

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  1. Billings-Gagliardi S., Adcock L. H., Wolf M. K. Hypomyelinated mutant mice: description of jpmsd and comparison with jp and qk on their present genetic backgrounds. Brain Res. 1980 Aug 4;194(2):325–338. doi: 10.1016/0006-8993(80)91215-9. [DOI] [PubMed] [Google Scholar]
  2. Chan D. S., Lees M. B. Gel electrophoresis studies of bovine brain white matter proteolipid and myelin proteins. Biochemistry. 1974 Jun 18;13(13):2704–2712. doi: 10.1021/bi00710a008. [DOI] [PubMed] [Google Scholar]
  3. Dautigny A., Alliel P. M., d'Auriol L., Pham Dinh D., Nussbaum J. L., Galibert F., Jollès P. Molecular cloning and nucleotide sequence of a cDNA clone coding for rat brain myelin proteolipid. FEBS Lett. 1985 Aug 19;188(1):33–36. doi: 10.1016/0014-5793(85)80869-3. [DOI] [PubMed] [Google Scholar]
  4. Dautigny A., Mattei M. G., Morello D., Alliel P. M., Pham-Dinh D., Amar L., Arnaud D., Simon D., Mattei J. F., Guenet J. L. The structural gene coding for myelin-associated proteolipid protein is mutated in jimpy mice. 1986 Jun 26-Jul 2Nature. 321(6073):867–869. doi: 10.1038/321867a0. [DOI] [PubMed] [Google Scholar]
  5. Eicher E. M., Hoppe P. C. Use of chimeras to transmit lethal genes in the mouse and to demonstrate allelism of the two X-linked male lethal genes jp and msd. J Exp Zool. 1973 Feb;183(2):181–184. doi: 10.1002/jez.1401830205. [DOI] [PubMed] [Google Scholar]
  6. Helynck G., Luu B., Nussbaum J. L., Picken D., Skalidis G., Trifilieff E., Van Dorsselaer A., Seta P., Sandeaux R., Gavach C. Brain proteolipids. Isolation, purification and effect on ionic permeability of membranes. Eur J Biochem. 1983 Jul 1;133(3):689–695. doi: 10.1111/j.1432-1033.1983.tb07518.x. [DOI] [PubMed] [Google Scholar]
  7. Kamholz J., de Ferra F., Puckett C., Lazzarini R. Identification of three forms of human myelin basic protein by cDNA cloning. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4962–4966. doi: 10.1073/pnas.83.13.4962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kozak C. A. Genetic mapping of a mouse chromosomal locus required for mink cell focus-forming virus replication. J Virol. 1983 Oct;48(1):300–303. doi: 10.1128/jvi.48.1.300-303.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Matthieu J. M., Widmer S., Herschkowitz Jimpy, an anomaly of, myelin maturation. Biochemical study of myelination phases. Brain Res. 1973 Jun 15;55(2):403–412. doi: 10.1016/0006-8993(73)90305-3. [DOI] [PubMed] [Google Scholar]
  10. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  11. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Milner R. J., Lai C., Nave K. A., Lenoir D., Ogata J., Sutcliffe J. G. Nucleotide sequences of two mRNAs for rat brain myelin proteolipid protein. Cell. 1985 Oct;42(3):931–939. doi: 10.1016/0092-8674(85)90289-2. [DOI] [PubMed] [Google Scholar]
  13. Molineaux S. M., Engh H., de Ferra F., Hudson L., Lazzarini R. A. Recombination within the myelin basic protein gene created the dysmyelinating shiverer mouse mutation. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7542–7546. doi: 10.1073/pnas.83.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Naismith A. L., Hoffman-Chudzik E., Tsui L. C., Riordan J. R. Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA. Nucleic Acids Res. 1985 Oct 25;13(20):7413–7425. doi: 10.1093/nar/13.20.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nave K. A., Lai C., Bloom F. E., Milner R. J. Jimpy mutant mouse: a 74-base deletion in the mRNA for myelin proteolipid protein and evidence for a primary defect in RNA splicing. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9264–9268. doi: 10.1073/pnas.83.23.9264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nussbaum J. L., Mandel P. Brain proteolipids in neurological mutant mice. Brain Res. 1973 Oct 26;61:295–310. doi: 10.1016/0006-8993(73)90534-9. [DOI] [PubMed] [Google Scholar]
  17. Roach A., Takahashi N., Pravtcheva D., Ruddle F., Hood L. Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell. 1985 Aug;42(1):149–155. doi: 10.1016/s0092-8674(85)80110-0. [DOI] [PubMed] [Google Scholar]
  18. SIDMAN R. L., DICKIE M. M., APPEL S. H. MUTANT MICE (QUAKING AND JIMPY) WITH DEFICIENT MYELINATION IN THE CENTRAL NERVOUS SYSTEM. Science. 1964 Apr 17;144(3616):309–311. doi: 10.1126/science.144.3616.309. [DOI] [PubMed] [Google Scholar]
  19. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  20. Shmookler Reis R. J., Biro P. A. Sequence and evolution of mouse satellite DNA. J Mol Biol. 1978 May 25;121(3):357–374. doi: 10.1016/0022-2836(78)90369-8. [DOI] [PubMed] [Google Scholar]
  21. Skoff R. P. Increased proliferation of oligodendrocytes in the hypomyelinated mouse mutant-jimpy. Brain Res. 1982 Sep 23;248(1):19–31. doi: 10.1016/0006-8993(82)91143-x. [DOI] [PubMed] [Google Scholar]
  22. Ting-Beall H. P., Lees M. B., Robertson J. D. Interactions of Folch-Lees proteolipid apoprotein with planar lipid bilayers. J Membr Biol. 1979 Dec 12;51(1):33–46. doi: 10.1007/BF01869342. [DOI] [PubMed] [Google Scholar]
  23. Trifilieff E., Luu B., Nussbaum J. L., Roussel G., Espinosa de los Monteros A., Sabatier J. M., Van Rietschoten J. A specific immunological probe for the major myelin proteolipid. Confirmation of a deletion in DM-20. FEBS Lett. 1986 Mar 31;198(2):235–239. doi: 10.1016/0014-5793(86)80412-4. [DOI] [PubMed] [Google Scholar]
  24. Vacher-Leprêtre M., Nicot C., Alfsen A., Jollès J., Jollès P. Study of the apoprotein of Folch-Pi bovine proteolipid. II. Characterization of the components isolated from sodium dodecyl sulfate solutions. Biochim Biophys Acta. 1976 Feb 20;420(2):323–331. doi: 10.1016/0005-2795(76)90324-x. [DOI] [PubMed] [Google Scholar]
  25. Willard H. F., Riordan J. R. Assignment of the gene for myelin proteolipid protein to the X chromosome: implications for X-linked myelin disorders. Science. 1985 Nov 22;230(4728):940–942. doi: 10.1126/science.3840606. [DOI] [PubMed] [Google Scholar]
  26. Winter E., Yamamoto F., Almoguera C., Perucho M. A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7575–7579. doi: 10.1073/pnas.82.22.7575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yanagisawa K., Quarles R. H. Jimpy mice: quantitation of myelin-associated glycoprotein and other proteins. J Neurochem. 1986 Jul;47(1):322–325. doi: 10.1111/j.1471-4159.1986.tb02866.x. [DOI] [PubMed] [Google Scholar]
  28. de Ferra F., Engh H., Hudson L., Kamholz J., Puckett C., Molineaux S., Lazzarini R. A. Alternative splicing accounts for the four forms of myelin basic protein. Cell. 1985 Dec;43(3 Pt 2):721–727. doi: 10.1016/0092-8674(85)90245-4. [DOI] [PubMed] [Google Scholar]

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