Advances in transgenic rat production

Filipiak, Wanda E.; Saunders, Thomas L.

doi:10.1007/s11248-006-9002-x

Cited by 88 publications

(70 citation statements)

References 46 publications

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“…With so many more models available for study in the rat, it makes one speculate whether the renal community should place more effort into producing transgenic rats for renal research. With the successful production of a renal-specific transgenic rat by Wharram et al (176) in 2005 and advances being made in producing transgenic rats (58), it is clear that this may be a worthy direction for the future.…”

Section: Discussionmentioning

confidence: 99%

Inducible rodent models of acquired podocyte diseases

Pippin

Brinkkoetter²,

Cormack-Aboud³

et al. 2009

American Journal of Physiology-Renal Physiology

236

263

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Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009. First published September 10, 2008 doi:10.1152/ajprenal.90421.2008.-Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.glomerulus; animal models HISTOLOGICAL ANALYSIS is a cornerstone for studying mechanisms of glomerular disease. However, analysis in human disease is limited by a relative paucity of tissue availability. Renal biopsies are only pursued if a presumptive diagnosis cannot be established on clinical grounds. Tissue sampling is typically restricted to the time of disease presentation and is rarely performed in follow-up, providing a mere snapshot of disease course.Animal models have significantly advanced our understanding of the pathogenesis of glomerular disease by overcoming these hurdles. Serial assessment of renal tissue in experimental models affords the opportunity to study development and progression of disease over time. Furthermore, the host response to injury may be deliberately modified, for example, through pharmacological intervention, selective disruption (knockout strategies), or overexpression (transgenic strategies) of a particular gene, allowing for mechanistic evaluations. A variety of animal species have been employed in the study of glomerular disease, but rodent models are preferred due to lower cost, maintenance requirements, and short gestational periods. Although both rats and mice are utilized, there are some important advantages and disadvantages for each (Table 1). The development of transgenic technology has proven an invaluable tool in elucidating the function of individual genes in health and disease. However, they cannot replace experimental models in furthering our understanding of the mechanisms...

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Section: Discussionmentioning

confidence: 99%

Inducible rodent models of acquired podocyte diseases

Pippin

Brinkkoetter²,

Cormack-Aboud³

et al. 2009

American Journal of Physiology-Renal Physiology

236

263

View full text Add to dashboard Cite

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“…Transgenic rats expressing transposases were generated using standard methods (Filipiak and Saunders 2006).…”

Section: Generation Of Transgenic Ratsmentioning

confidence: 99%

Insertional Mutagenesis by a Hybrid PiggyBac and Sleeping Beauty Transposon in the Rat

et al. 2012

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A hybrid piggyBac/Sleeping Beauty transposon-based insertional mutagenesis system that can be mobilized by simple breeding was established in the rat. These transposons were engineered to include gene trap sequences and a tyrosinase (Tyr) pigmentation reporter to rescue the albinism of the genetic background used in the mutagenesis strategy. Single-copy transposon insertions were transposed into the rat genome by co-injection of plasmids carrying the transposon and RNA encoding piggyBac transposase into zygotes. The levels of transgenic Tyr expression were influenced by chromosomal context, leading to transgenic rats with different pigmentation that enabled visual genotyping. Transgenic rats designed to ubiquitously express either piggyBac or Sleeping Beauty transposase were generated by standard zygote injection also on an albino background. Bigenic rats carrying single-copy transposons at known loci and transposase transgenes exhibited coat color mosaicism, indicating somatic transposition. PiggyBac or Sleeping Beauty transposase bigenic rats bred with wild-type albino rats yielded offspring with pigmentation distinct from the initial transposon insertions as a consequence of germline transposition to new loci. The germline transposition frequency for Sleeping Beauty and piggyBac was 10% or about one new insertion per litter. Approximately 50% of the insertions occurred in introns. Chimeric transcripts containing endogenous and gene trap sequences were identified in Gabrb1 mutant rats. This mutagenesis system based on simple crosses and visual genotyping can be used to generate a collection of single-gene mutations in the rat.

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“…Microinjection technique has been used in transgenic animals for many years (Bishop & Smith, 1989;Chan & Yang, 2009;Charreau et al, 1996;Filipiak & Saunders, 2006;Ménoret et al, 2010;Tesson et al, 2005;Yang et al, 2008). Microinjection technique also has been used as a tool to clone animals-first, an unfertilized egg's nucleus is removed; then a nucleus of a somatic cell is microinjected into the denucleated egg; now the egg contains a whole copy of the diploid genomic DNA from the somatic cell and can be cultured in vitro to form a blastocyst; and the blastocyst is implanted into the womb of an animal; eventually a cloned animal is born (Campbell et al, 1996;Vajta & Gjerris, 2006;Willadsen, 1986;Wilmut et al, 1997).…”

Section: Microinjectionmentioning

confidence: 99%

Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients

Song¹

2011

Non-Viral Gene Therapy

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Advances in transgenic rat production

Cited by 88 publications

References 46 publications

Inducible rodent models of acquired podocyte diseases

Inducible rodent models of acquired podocyte diseases

Insertional Mutagenesis by a Hybrid PiggyBac and Sleeping Beauty Transposon in the Rat

Gene Therapy of Some Genetic Diseases by Transferring Normal Human Genomic DNA into Somatic Cells and Stem Cells from Patients

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