Transgenic Research

, Volume 18, Issue 4, pp 545–558

Hemizygous minipigs produced by random gene insertion and handmade cloning express the Alzheimer’s disease-causing dominant mutation APPsw

  • Peter M. Kragh
  • Anders Lade Nielsen
  • Juan Li
  • Yutao Du
  • Lin Lin
  • Mette Schmidt
  • Ingrid Brück Bøgh
  • Ida E. Holm
  • Jannik E. Jakobsen
  • Marianne G. Johansen
  • Stig Purup
  • Lars Bolund
  • Gábor Vajta
  • Arne Lund Jørgensen
Original Paper

DOI: 10.1007/s11248-009-9245-4

Cite this article as:
Kragh, P.M., Nielsen, A.L., Li, J. et al. Transgenic Res (2009) 18: 545. doi:10.1007/s11248-009-9245-4

Abstract

In an effort to develop a porcine model of Alzheimer’s disease we used handmade cloning to produce seven transgenic Göttingen minipigs. The donor fibroblasts had been stably transfected with a plasmid cassette containing, as transgene, the cDNA of the neuronal variant of the human amyloid precursor protein gene with the Swedish mutation preceded by beta-globin sequences to induce splicing and a human PDGFbeta promoter fragment to drive transcription. Transgene insertion had occurred only at the GLIS3 locus where a single complete copy of the transgene was identified in intronic sequences in opposite direction. Similar and robust levels of the transgene transcript were detected in skin biopsies from all piglets and the sequence of full-length transcript was verified. Consistent with PDGFbeta promoter function, high levels of transgene expression, including high level of the corresponding protein, was observed in brain tissue and not in heart or liver tissues. A rough estimate predicts that accumulation of the Aβ peptide in the brain may develop at the age of 1–2 years.

Keywords

Animal models Porcine Transgenesis Handmade cloning Alzheimer’s disease 

Abbreviations

APP

Amyloid precursor protein

APP695sw

Neuronal splicevariant of APP with the Swedish mutation

Amyloid beta-protein

AD

Alzheimer’s disease

PSEN

Presenilin

NFT

Neurofibrillary tangles

HMC

Handmade cloning

SCNT

Somatic cell nuclear transfer

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Peter M. Kragh
    • 1
    • 2
  • Anders Lade Nielsen
    • 1
  • Juan Li
    • 2
  • Yutao Du
    • 2
  • Lin Lin
    • 2
  • Mette Schmidt
    • 3
  • Ingrid Brück Bøgh
    • 3
    • 4
  • Ida E. Holm
    • 5
  • Jannik E. Jakobsen
    • 1
  • Marianne G. Johansen
    • 1
  • Stig Purup
    • 6
  • Lars Bolund
    • 1
  • Gábor Vajta
    • 2
    • 7
  • Arne Lund Jørgensen
    • 1
  1. 1.Department of Human Genetics, Faculty of Health Sciences, The Bartholin BuildingAarhus UniversityAarhus CDenmark
  2. 2.Department of Genetics and Biotechnology, Faculty of Agricultural SciencesAarhus UniversityTjeleDenmark
  3. 3.Department of Veterinary Reproduction and Obstetrics, Faculty of Life SciencesUniversity of CopenhagenFrederiksberg CDenmark
  4. 4.MåløvDenmark
  5. 5.Department of Pathology, Aalborg HospitalAarhus University HospitalAalborgDenmark
  6. 6.Department of Animal Health, Welfare and Nutrition, Faculty of Agricultural SciencesAarhus UniversityTjeleDenmark
  7. 7.Leederville, PerthAustralia

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