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. 1989 May;86(10):3709–3712. doi: 10.1073/pnas.86.10.3709

Insertional mutation in a transgenic mouse allelic with Purkinje cell degeneration.

T F Krulewski 1, P E Neumann 1, J W Gordon 1
PMCID: PMC287209  PMID: 2726749

Abstract

Purkinje cell degeneration (pcd) is an autosomal recessive mutation which maps to chromosome 13 in the mouse. The pcd mutation causes loss of cerebellar Purkinje cells, retinal photoreceptor cells, and olfactory bulb mitral cells, as well as abnormalities of spermatogenesis. pcd is among a number of autosomal recessive mutations in mice and humans that affect neurologic function and male fertility. The cloning of one or more of these loci would contribute significantly to our understanding of the genetic control of development and maintenance of affected cell types. We report here identification of a transgenic mouse line with an insertional mutation that is allelic with pcd and manifests histopathologic features indistinguishable from those of the spontaneous mutation. The creation of an allele of pcd by transgene insertion should make possible the cloning of the pcd locus.

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Selected References

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

  1. Breindl M., Harbers K., Jaenisch R. Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure. Cell. 1984 Aug;38(1):9–16. doi: 10.1016/0092-8674(84)90521-x. [DOI] [PubMed] [Google Scholar]
  2. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  3. Gordon J. W. A foreign dihydrofolate reductase gene in transgenic mice acts as a dominant mutation. Mol Cell Biol. 1986 Jun;6(6):2158–2167. doi: 10.1128/mcb.6.6.2158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gordon J. W., Scangos G. A., Plotkin D. J., Barbosa J. A., Ruddle F. H. Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7380–7384. doi: 10.1073/pnas.77.12.7380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Harbers K., Kuehn M., Delius H., Jaenisch R. Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1504–1508. doi: 10.1073/pnas.81.5.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hartung S., Jaenisch R., Breindl M. Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. 1986 Mar 27-Apr 2Nature. 320(6060):365–367. doi: 10.1038/320365a0. [DOI] [PubMed] [Google Scholar]
  7. Jaenisch R. Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1260–1264. doi: 10.1073/pnas.73.4.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jaenisch R., Harbers K., Schnieke A., Löhler J., Chumakov I., Jähner D., Grotkopp D., Hoffmann E. Germline integration of moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death. Cell. 1983 Jan;32(1):209–216. doi: 10.1016/0092-8674(83)90511-1. [DOI] [PubMed] [Google Scholar]
  9. Kothary R., Clapoff S., Brown A., Campbell R., Peterson A., Rossant J. A transgene containing lacZ inserted into the dystonia locus is expressed in neural tube. Nature. 1988 Sep 29;335(6189):435–437. doi: 10.1038/335435a0. [DOI] [PubMed] [Google Scholar]
  10. Mark W. H., Signorelli K., Lacy E. An insertional mutation in a transgenic mouse line results in developmental arrest at day 5 of gestation. Cold Spring Harb Symp Quant Biol. 1985;50:453–463. doi: 10.1101/sqb.1985.050.01.057. [DOI] [PubMed] [Google Scholar]
  11. McNeish J. D., Scott W. J., Jr, Potter S. S. Legless, a novel mutation found in PHT1-1 transgenic mice. Science. 1988 Aug 12;241(4867):837–839. doi: 10.1126/science.3406741. [DOI] [PubMed] [Google Scholar]
  12. Mullen R. J., Eicher E. M., Sidman R. L. Purkinje cell degeneration, a new neurological mutation in the mouse. Proc Natl Acad Sci U S A. 1976 Jan;73(1):208–212. doi: 10.1073/pnas.73.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mullen R. J., LaVail M. Two types of retinal degeneration in cerebellar mutant mice. Nature. 1975 Dec 11;258(5535):528–530. doi: 10.1038/258528a0. [DOI] [PubMed] [Google Scholar]
  14. Palmiter R. D., Wilkie T. M., Chen H. Y., Brinster R. L. Transmission distortion and mosaicism in an unusual transgenic mouse pedigree. Cell. 1984 Apr;36(4):869–877. doi: 10.1016/0092-8674(84)90036-9. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Simonsen C. C., Levinson A. D. Isolation and expression of an altered mouse dihydrofolate reductase cDNA. Proc Natl Acad Sci U S A. 1983 May;80(9):2495–2499. doi: 10.1073/pnas.80.9.2495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  18. Wagner E. F., Covarrubias L., Stewart T. A., Mintz B. Prenatal lethalities in mice homozygous for human growth hormone gene sequences integrated in the germ line. Cell. 1983 Dec;35(3 Pt 2):647–655. doi: 10.1016/0092-8674(83)90097-1. [DOI] [PubMed] [Google Scholar]
  19. Woychik R. P., Stewart T. A., Davis L. G., D'Eustachio P., Leder P. An inherited limb deformity created by insertional mutagenesis in a transgenic mouse. Nature. 1985 Nov 7;318(6041):36–40. doi: 10.1038/318036a0. [DOI] [PubMed] [Google Scholar]

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