Development of new inbred transgenic strains of rats with LacZ or GFP

Inoue, Hirokazu; Ohsawa, Ichiro; Murakami, Takashi; Kimura, Atsushi; Hakamata, Yoji; Sato, Yuki; Kaneko, Takashi; Takahashi, Masafumi; Okada, Takashi; Ozawa, Keiya; Francis, Jeremy S.; Leone, Paola; Kobayashi, Eiji

doi:10.1016/j.bbrc.2005.01.132

Cited by 109 publications

(116 citation statements)

References 30 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…An immune response to GFP has been observed in adult mice, 22 rats 23 and baboons, 24 which suggests that GFP is an immunogenic protein. We did not observe antibodies to GFP in animals injected in utero, or at the day of birth, with GFP vectors.…”

Section: Discussionmentioning

confidence: 98%

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Seppen¹,

Til²,

Rijt³

et al. 2005

Gene Ther

View full text Add to dashboard Cite

Gene therapy for inherited disorders might cause an immune response to the therapeutic protein. A solution would be to introduce the gene in the fetal or neonatal period, which should lead to tolerization. Lentiviral vectors mediate long-term gene expression, and are well suited for gene therapy early in development. A model for fetal or neonatal gene therapy is the inherited disorder of bilirubin metabolism, Crigler-Najjar disease (CN). The absence of bilirubin UDP-glucoronyltransferase (UGT1A1) activity in CN patients causes high serum levels of unconjugated bilirubin and brain damage in infancy. CN is attractive for the development of gene therapy because the mutant Gunn rat closely mimics the human disease.Injection of UGT1A1 lentiviral vectors corrected the hyperbilirubinemia for more than a year in rats injected as fetuses and for up to 18 weeks in rats injected the day of birth. UGT1A1 gene transfer was confirmed by the presence of bilirubin glucuronides in bile. All animals injected with UGT1A1 lentiviral vectors developed antibodies to UGT1A1. Animals injected with green fluorescent protein (GFP) lentiviral vectors did not develop antibodies to GFP. Our results indicate that fetal and neonatal gene therapy with immunogenic proteins such as UGT1A1 does not necessarily lead to tolerization.

show abstract

Section: Discussionmentioning

confidence: 98%

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Seppen¹,

Til²,

Rijt³

et al. 2005

Gene Ther

View full text Add to dashboard Cite

show abstract

“…hMSCs were used within three passages to avoid phenotypic changes. The Luc/LacZ-dual-Tg rat was established by mating the Luc-rat and the LacZ-rat [15,16]. Rat MSCs were established and maintained as described elsewhere [17].…”

Section: Culture and Manipulation Of Human And Rat Mscs And Human Endmentioning

confidence: 99%

Xenotransplanted Embryonic Kidney Provides a Niche for Endogenous Mesenchymal Stem Cell Differentiation into Erythropoietin-Producing Tissue

et al. 2012

Self Cite

View full text Add to dashboard Cite

Recent findings have demonstrated that stem cells can differentiate into mature tissue when supplied with a niche containing factors identical to those in the normal developmental program. A niche for the development of an organ can be provided by xenotransplantation of a similar developing organ. However, this process has many technical, safety, and ethical concerns. Here, we established xenotransplantation models that control endogenous mesenchymal stem cell (MSC) differentiation into mature erythropoietin (EPO)-producing tissue in a niche provided by a developing xenometanephros. Transplantation of rat metanephroi into mouse omentum, and similarly pig metanephroi into cat omentum, led to the recruitment of host cells and EPO production. EPO-expressing cells were not differentiated from integrating vessels because they did not coexpress endothelial markers (Tie-2 and VE-cadherin). Instead, EPOexpressing cells were shown to be derived from circulating host cells, as shown by enhanced green fluorescent protein (EGFP) expression in the grown transplants of chimeric mice bearing bone marrow from a transgenic mouse expressing EGFP under the control of the EPO promoter. These results suggest that donor cell recruitment and differentiation in a xenotransplanted developing organ may be consistent between species. The cells responsible for EPO expression were identified as MSCs by injecting human bone marrow-derived MSCs and endothelial progenitor cells into NOD/SCID mice. Furthermore, using metanephroi from transgenic ER-E2F1 suicide-inducible mice, the xenotissue component could be eliminated, leaving autologous EPO-producing tissue. Our findings may alleviate adverse effects due to long-lasting immunosuppression and help mitigate ethical concerns.

show abstract

“…In rodents, transgenic animals expressing such cell markers as green fluorescent protein (GFP), red fluorescent protein (RFP) and β-galactosidase have been produced, making rodents useful in a wide range of research [57,[59][60][61][62][63]. In addition, transgenic mice harboring a fluorescent ubiquitination-based cell-cycle indicator (Fucci) have recently been developed [64].…”

Section: Development Of Transgenic Pigs With Reporter Genesmentioning

confidence: 99%

“…These cloned animals could provide a useful model for donors and recipients of syngeneic background. However, the immunogenicity of fluorescent proteins may hamper long-term tracking of cells and tissues in transplantation experiments [61]. In contrast, β-galactosidase is less immunogenic than fluorescent protein [61] and may thus be a better candidate for transplantation studies.…”

Section: Development Of Transgenic Pigs With Reporter Genesmentioning

confidence: 99%

Application of Genetically Modified and Cloned Pigs in Translational Research

Matsunari

Nagashima

2009

Journal of Reproduction and Development

View full text Add to dashboard Cite

Abstract. Pigs are increasingly being recognized as good large-animal models for translational research, linking basic science to clinical applications in order to establish novel therapeutics. This article reviews the current status and future prospects of genetically modified and cloned pigs in translational studies. It also highlights pigs specially designed as disease models, for xenotransplantation or to carry cell marker genes. Finally, use of porcine somatic stem and progenitor cells in preclinical studies of cell transplantation therapy is also discussed. Key words: Cloned pig, Gene knockout, Transgenic pig, Translational research (J. Reprod. Dev. 55: [225][226][227][228][229][230] 2009) t present, pigs are not only considered important livestock but are also essential large-animal models in various types of biomedical research [1][2][3][4][5][6]. Furthermore, due to recent technological advances in genetic modification and somatic cell cloning, the range of applications for porcine models has increased markedly [7][8][9][10][11][12][13][14]. The present review focuses on development of genetically modified and cloned pigs and their use in translational studies.Translational research plays an important role as a bridge between basic science outcomes and the clinical realm, leading to development of novel therapeutics. However, disparate findings for rodent models and humans have hindered the translation of rodent data into actionable technologies for patients [15]. In contrast, pigs have many anatomical and physiological similarities to humans, including their cardiovascular systems, omnivorous gastrointestinal tracts and central nervous systems. Their physical sizes are also more comparable to that of humans, rendering pigs more appropriate for development of new surgical or endoscopic techniques.In the future, more advanced translational research may be conducted by improving the clinical relevance of pig models through genetic engineering. This article reviews the current status and future prospects of genetically modified pigs in preclinical studies of stem and progenitor cell therapy, the development of disease models and xenotransplantation.

show abstract

Development of new inbred transgenic strains of rats with LacZ or GFP

Cited by 109 publications

References 30 publications

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats

Xenotransplanted Embryonic Kidney Provides a Niche for Endogenous Mesenchymal Stem Cell Differentiation into Erythropoietin-Producing Tissue

Application of Genetically Modified and Cloned Pigs in Translational Research

Contact Info

Product

Resources

About