Abstract
So far no systematic studies have been conducted to investigate developmental aberrations after prenatal gene transfer in mice. Here, we suggest procedures for such observations to be applied, tested and improved in further in utero gene therapy experiments. They are based on our own experience in husbandry for transgenic human diseases mouse models and breading, rearing, and observing mice after fetal gene transfer as well as on the systematic screens for monitoring of knock-out mutant mouse phenotypes established in international mutagenesis projects (EUMORPHIA and EUMODIC and subsequently the International Mouse Phenotyping Consortium).
We also describe here the analysis procedures for detection of germ line mutations based on quantitative PCR (qPCR) by sperm-DNA analysis and breeding studies.
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References
Rosenthal N, Brown SDM (2007) The mouse ascending: perspectives for human disease models. Nat Cell Biol 9:997–999
Gonzaga S, Henriques-Coelho T, Davey M et al (2008) Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung. Am J Respir Cell Mol Biol 39: 346–355
Tarantal AF, Chen H, Shi TT et al (2010) Overexpression of TGF-{beta}1 in foetal monkey lung results in prenatal pulmonary fibrosis. Eur Respir J 36(4):907–914
Gates H, Mallon AM, Brown SDM (2010) High-throughput mouse phenotyping. Methods 53:394–404
Porada CD, Park PJ, Tellez J et al (2005) Male germ-line cells are at risk following direct-injection retroviral-mediated gene transfer in utero. Mol Ther 12:754–762
Ye X, Gao GP, Pabin C, Raper SE, Wilson JM (1998) Evaluating the potential of germ line transmission after intravenous administration of recombinant adenovirus in the C3H mouse. Hum Gene Ther 9:2135–2142
Schuettrumpf J, Liu JH, Couto LB et al (2006) Inadvertent germline transmission of AAV2 vector: findings in a rabbit model correlate with those in a human clinical trial. Mol Ther 13: 1064–1073
Park PJ, Colletti E, Ozturk F et al (2009) Factors determining the risk of inadvertent retroviral transduction of male germ cells after in utero gene transfer in sheep. Hum Gene Ther 20:201–215
Lee CC, Jimenez DF, Kohn DB, Tarantal AF (2005) Fetal gene transfer using lentiviral vectors and the potential for germ cell transduction in rhesus monkeys (Macaca mulatta). Hum Gene Ther 16:417–425
Kazazian H (1999) An estimated frequency of endogenous insertional mutations in humans. Nat Genet 22:130
Hossain AM, Rizk B, Behzadian A, Thorneycroft (1997) Modified guanidinium thiocyanate method for human sperm DNA isolation. Mol Hum Reprod 3:953–956
Wang LJ, Chen YM, George D et al (2002) Engraftment assessment in human and mouse liver tissue after sex-mismatched liver cell transplantation by real-time quantitative PCR for Y chromosome sequences. Liver Transpl 8:822–828
Acknowledgements
We wish to thank Paul Potter and Andrew Blake for introducing us to the International Mouse Phenotyping project and for helpful comments.
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Coutelle, C., Waddington, S.N., Themis, M. (2012). Monitoring for Potential Adverse Effects of Prenatal Gene Therapy: Mouse Models for Developmental Aberrations and Inadvertent Germ Line Transmission. In: Coutelle, C., Waddington, S. (eds) Prenatal Gene Therapy. Methods in Molecular Biology, vol 891. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-873-3_15
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DOI: https://doi.org/10.1007/978-1-61779-873-3_15
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