Mammalian Genome

, Volume 19, Issue 1, pp 26–31 | Cite as

Characterization of the ETnII-α endogenous retroviral element in the BALB/cJ Zhx2Afr1 allele

  • Sudhir Perincheri
  • David K. Peyton
  • Michelle Glenn
  • Martha L. Peterson
  • Brett T. Spear
Article

Abstract

Integration of mouse endogenous retroviral (MERV) elements is responsible for an estimated 10% of spontaneous mutations that have been characterized in the laboratory mouse. We recently identified a MERV integration in the first intron of the Zinc fingers and homeoboxes 2 (Zhx2) gene in BALB/cJ mice, resulting in reduced Zhx2 expression. This integration is found in BALB/cJ but not in other BALB/c substrains, indicating that it occurred after these substrains separated in the late 1930s. We have characterized this MERV element and show here that it belongs to the ETnII-α class of elements. Our analysis reveals that the Zhx2 ETn element lacks a 69-bp sequence compared to most other ETn elements which may be due to recombination between two identical 13-bp elements. Three mature Zhx2 transcripts are found in the liver of BALB/cJ mice. The major transcript is spliced from Zhx2 exon 1 to the 5′ ETn LTR and is polyadenylated at the 3′ LTR. Of the two less abundant transcripts, one is identical to the wild-type transcript, whereas the second contains 183 bp of ETn sequence spliced between Zhx2 exons 1 and 2. We have also sequenced and analyzed products from the faslpr ETn found in MRL/lpr mice and show that it belongs to the ETnII-β class of elements.

References

  1. Adachi M, Watanabe-Fukunaga R, Nagata S (1993) Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A 90:1756–1760PubMedCrossRefGoogle Scholar
  2. Bannert N, Kurth R (2004) Retroelements and the human genome: new perspectives on an old relation. Proc Natl Acad Sci U S A 101(Suppl 2):14572–14579PubMedCrossRefGoogle Scholar
  3. Baust C, Gagnier L, Baillie GJ, Harris MJ, Juriloff DM, et al. (2003) Structure and expression of mobile ETnII retroelements and their coding-competent MusD relatives in the mouse. J Virol 77:11448–11458PubMedCrossRefGoogle Scholar
  4. Belayew A, Tilghman SM (1982) Genetic analysis of α-fetoprotein synthesis in mice. Mol Cell Biol 2:1427–1435PubMedGoogle Scholar
  5. Blankenhorn EP, Duncan R, Huppi C, Potter M (1988) Chromosomal location of the regulator of mouse α-fetoprotein, afr-1. Genetics 119:687–691PubMedGoogle Scholar
  6. Chu JL, Drappa J, Parnassa A, Elkon KB (1993) The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J Exp Med 178:723–730PubMedCrossRefGoogle Scholar
  7. Cohen PL, Eisenberg RA (1991) Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269PubMedCrossRefGoogle Scholar
  8. Kobayashi S, Hirano T, Kakinuma M, Uede T (1993) Transcriptional repression and differential splicing of Fas mRNA by early transposon (ETn) insertion in autoimmune lpr mice. Biochem Biophys Res Commun 191:617–624PubMedCrossRefGoogle Scholar
  9. Laird PW, Zijderveld A, Linders K, Rudnicki MA, Jaenisch R, et al. (1991) Simplified mammalian DNA isolation procedure. Nucleic Acids Res 19:4293PubMedCrossRefGoogle Scholar
  10. Maksakova IA, Romanish MT, Gagnier L, Dunn CA, van de Lagemaat LN, et al. (2006) Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line. PLoS Genet 2:e2PubMedCrossRefGoogle Scholar
  11. Olsson M, Lindahl G, Roushlahti E (1977) Genetic control of alpha-fetoprotein synthesis in the mouse. J Exp Med 145:819–830PubMedCrossRefGoogle Scholar
  12. Perincheri S, Dingle RW, Peterson ML, Spear BT (2005) Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene. Proc Natl Acad Sci U S A 102:396–401PubMedCrossRefGoogle Scholar
  13. Potter M (1985) History of the BALB/c family. Curr Top Microbiol Immunol 122:1–5PubMedGoogle Scholar
  14. Ribet D, Dewannieux M, Heidmann T (2004) An active murine transposon family pair: retrotransposition of “master” MusD copies and ETn trans-mobilization. Genome Res 14:2261–2267PubMedCrossRefGoogle Scholar
  15. Spear BT (1999) Alpha-fetoprotein gene regulation: Lessons from transgenic mice. Semin Cancer Biol 9:109–116PubMedCrossRefGoogle Scholar
  16. Spear BT, Jin L, Ramasamy S, Dobierzewska A (2006) Transcriptional control in the mammalian liver: liver development, perinatal repression, and zonal gene regulation. Cell Mol Life Sci 63:2922–2938PubMedCrossRefGoogle Scholar
  17. Thien H, Ruther U (1999) The mouse mutation Pdn (Polydactyly Nagoya) is caused by the integration of a retrotransposon into the Gli3 gene. Mamm Genome 10:205–209PubMedCrossRefGoogle Scholar
  18. White RA, McNulty SG, Nsumu NN, Boydston LA, Brewer BP, et al. (2005) Positional cloning of the Ttc7 gene required for normal iron homeostasis and mutated in hea and fsn anemia mice. Genomics 85:330–337PubMedCrossRefGoogle Scholar
  19. Wu J, Zhou T, He J, Mountz JD (1993) Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med 178:461–468PubMedCrossRefGoogle Scholar
  20. Zhang Q, Li W, Novak EK, Karim A, Mishra VS, et al. (2002) The gene for the muted (mu) mouse, a model for Hermansky-Pudlak syndrome, defines a novel protein which regulates vesicle trafficking. Hum Mol Genet 11:697–706PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Sudhir Perincheri
    • 1
    • 5
  • David K. Peyton
    • 2
  • Michelle Glenn
    • 1
  • Martha L. Peterson
    • 1
    • 3
  • Brett T. Spear
    • 1
    • 3
    • 4
  1. 1.Department of MicrobiologyImmunology and Molecular Genetics, University of Kentucky College of MedicineLexingtonUSA
  2. 2.Department of Biological and Environmental SciencesMorehead State UniversityMoreheadUSA
  3. 3.Markey Cancer CenterUniversity of Kentucky College of MedicineLexingtonUSA
  4. 4.Department of Microbiology, Immunology and Molecular Genetics, 210 Combs BuildingMarkey Cancer Center, University of Kentucky College of MedicineLexingtonUSA
  5. 5.Department of Genetics and DevelopmentColumbia UniversityNew YorkUSA

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