Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Jul;17(7):4080–4086. doi: 10.1128/mcb.17.7.4080

Proviral inactivation of the Npat gene of Mpv 20 mice results in early embryonic arrest.

M Di Fruscio 1, H Weiher 1, B C Vanderhyden 1, T Imai 1, T Shiomi 1, T A Hori 1, R Jaenisch 1, D A Gray 1
PMCID: PMC232261  PMID: 9199343

Abstract

The Mpv 20 transgenic mouse strain was created by infection of embryos with a defective retrovirus. When Mpv 20 heterozygous animals were crossed, no homozygous neonatal mice or midgestation embryos were identified. When embryos from heterozygous crosses were cultured in vitro, approximately one quarter arrested as uncompacted eight-cell embryos, indicating that proviral insertion resulted in a recessive lethal defect whose phenotype was manifest very early in development. Molecular cloning of the Mpv 20 insertion site revealed that the provirus had disrupted the Npat gene, a gene of unknown function, resulting in the production of a truncated Npat mRNA. Expression of the closely linked Atm gene was found to be unaffected by the provirus.

Full Text

The Full Text of this article is available as a PDF (591.8 KB).

Selected References

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

  1. Barker D. D., Wu H., Hartung S., Breindl M., Jaenisch R. Retrovirus-induced insertional mutagenesis: mechanism of collagen mutation in Mov13 mice. Mol Cell Biol. 1991 Oct;11(10):5154–5163. doi: 10.1128/mcb.11.10.5154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chatot C. L., Ziomek C. A., Bavister B. D., Lewis J. L., Torres I. An improved culture medium supports development of random-bred 1-cell mouse embryos in vitro. J Reprod Fertil. 1989 Jul;86(2):679–688. doi: 10.1530/jrf.0.0860679. [DOI] [PubMed] [Google Scholar]
  3. Chen Z., Friedrich G. A., Soriano P. Transcriptional enhancer factor 1 disruption by a retroviral gene trap leads to heart defects and embryonic lethality in mice. Genes Dev. 1994 Oct 1;8(19):2293–2301. doi: 10.1101/gad.8.19.2293. [DOI] [PubMed] [Google Scholar]
  4. Cheng S. S., Costantini F. Morula decompaction (mdn), a preimplantation recessive lethal defect in a transgenic mouse line. Dev Biol. 1993 Mar;156(1):265–277. doi: 10.1006/dbio.1993.1075. [DOI] [PubMed] [Google Scholar]
  5. DeGregori J., Russ A., von Melchner H., Rayburn H., Priyaranjan P., Jenkins N. A., Copeland N. G., Ruley H. E. A murine homolog of the yeast RNA1 gene is required for postimplantation development. Genes Dev. 1994 Feb 1;8(3):265–276. doi: 10.1101/gad.8.3.265. [DOI] [PubMed] [Google Scholar]
  6. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  7. Gray D. A. Insertional mutagenesis: neoplasia arising from retroviral integration. Cancer Invest. 1991;9(3):295–304. doi: 10.3109/07357909109021327. [DOI] [PubMed] [Google Scholar]
  8. Gridley T., Gray D. A., Orr-Weaver T., Soriano P., Barton D. E., Francke U., Jaenisch R. Molecular analysis of the Mov 34 mutation: transcript disrupted by proviral integration in mice is conserved in Drosophila. Development. 1990 May;109(1):235–242. doi: 10.1242/dev.109.1.235. [DOI] [PubMed] [Google Scholar]
  9. Gupta K., Chevrette M., Gray D. A. The Unp proto-oncogene encodes a nuclear protein. Oncogene. 1994 Jun;9(6):1729–1731. [PubMed] [Google Scholar]
  10. 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]
  11. Harbers K., Müller U., Grams A., Li E., Jaenisch R., Franz T. Provirus integration into a gene encoding a ubiquitin-conjugating enzyme results in a placental defect and embryonic lethality. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12412–12417. doi: 10.1073/pnas.93.22.12412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Imai T., Yamauchi M., Seki N., Sugawara T., Saito T., Matsuda Y., Ito H., Nagase T., Nomura N., Hori T. Identification and characterization of a new gene physically linked to the ATM gene. Genome Res. 1996 May;6(5):439–447. doi: 10.1101/gr.6.5.439. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Jähner D., Jaenisch R. Integration of Moloney leukaemia virus into the germ line of mice: correlation between site of integration and virus activation. Nature. 1980 Oct 2;287(5781):456–458. doi: 10.1038/287456a0. [DOI] [PubMed] [Google Scholar]
  15. Jähner D., Jaenisch R. Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature. 1985 Jun 13;315(6020):594–597. doi: 10.1038/315594a0. [DOI] [PubMed] [Google Scholar]
  16. Lewis S. E. Developmental analysis of lethal effects of homozygosity for the c25H deletion in the mouse. Dev Biol. 1978 Aug;65(2):553–557. doi: 10.1016/0012-1606(78)90052-0. [DOI] [PubMed] [Google Scholar]
  17. Matsuda Y., Imai T., Shiomi T., Saito T., Yamauchi M., Fukao T., Akao Y., Seki N., Ito H., Hori T. A. Comparative genome mapping of the ataxia-telangiectasia region in mouse, rat, and Syrian hamster. Genomics. 1996 Jun 15;34(3):347–352. doi: 10.1006/geno.1996.0297. [DOI] [PubMed] [Google Scholar]
  18. Riethmacher D., Brinkmann V., Birchmeier C. A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):855–859. doi: 10.1073/pnas.92.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rohdewohld H., Weiher H., Reik W., Jaenisch R., Breindl M. Retrovirus integration and chromatin structure: Moloney murine leukemia proviral integration sites map near DNase I-hypersensitive sites. J Virol. 1987 Feb;61(2):336–343. doi: 10.1128/jvi.61.2.336-343.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schnieke A., Harbers K., Jaenisch R. Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene. 1983 Jul 28-Aug 3Nature. 304(5924):315–320. doi: 10.1038/304315a0. [DOI] [PubMed] [Google Scholar]
  21. Seliger B., Kollek R., Stocking C., Franz T., Ostertag W. Viral transfer, transcription, and rescue of a selectable myeloproliferative sarcoma virus in embryonal cell lines: expression of the mos oncogene. Mol Cell Biol. 1986 Jan;6(1):286–293. doi: 10.1128/mcb.6.1.286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shirayoshi Y., Okada T. S., Takeichi M. The calcium-dependent cell-cell adhesion system regulates inner cell mass formation and cell surface polarization in early mouse development. Cell. 1983 Dec;35(3 Pt 2):631–638. doi: 10.1016/0092-8674(83)90095-8. [DOI] [PubMed] [Google Scholar]
  23. Soriano P., Gridley T., Jaenisch R. Retroviruses and insertional mutagenesis in mice: proviral integration at the Mov 34 locus leads to early embryonic death. Genes Dev. 1987 Jun;1(4):366–375. doi: 10.1101/gad.1.4.366. [DOI] [PubMed] [Google Scholar]
  24. Tsurumi C., DeMartino G. N., Slaughter C. A., Shimbara N., Tanaka K. cDNA cloning of p40, a regulatory subunit of the human 26S proteasome, and a homolog of the Mov-34 gene product. Biochem Biophys Res Commun. 1995 May 16;210(2):600–608. doi: 10.1006/bbrc.1995.1701. [DOI] [PubMed] [Google Scholar]
  25. Tsuzuki T., Fujii Y., Sakumi K., Tominaga Y., Nakao K., Sekiguchi M., Matsushiro A., Yoshimura Y., MoritaT Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6236–6240. doi: 10.1073/pnas.93.13.6236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vijaya S., Steffen D. L., Robinson H. L. Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. J Virol. 1986 Nov;60(2):683–692. doi: 10.1128/jvi.60.2.683-692.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weiher H., Noda T., Gray D. A., Sharpe A. H., Jaenisch R. Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome. Cell. 1990 Aug 10;62(3):425–434. doi: 10.1016/0092-8674(90)90008-3. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES