Targeted Genetic Modification: Xenotransplantation And Beyond

Prather, Randall S.

doi:10.1089/clo.2006.0085

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…In this article, we have shown that caffeine can rescue centrosome deterioration in aging oocytes using the porcine system as representative for most mammalian reproductive cell systems [Prather, 2007;Schatten, 2008]. We showed that the centrosome proteins g-tubulin and NuMA remain in similar configurations in aged caffeine-treated oocytes as seen in fresh oocytes, whereas oocytes aged without caffeine displayed centrosome deterioration, microtubule disorganization, and chromosome misalignment.…”

Section: Discussionmentioning

confidence: 90%

Centrosome abnormalities during porcine oocyte aging

Miao

Sun

Zhang

et al. 2009

Environ and Mol Mutagen

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Centrosomes are critically important for maintaining meiotic spindle integrity in the meiosis II (MII) stage where oocytes are arrested in most mammalian species before fertilization takes place. In women of advanced ages or during in vitro fertilization (IVF) procedures, aneuploidy is frequently seen as a result of oocyte aging, which is strongly related to centrosome instability. Abnormal distribution of centrosomes and microtubules has been reported in aging human and mouse oocytes. This study reports the dynamic changes of centrosomes and the microtubule cytoskeleton in porcine oocytes during aging and treatment by caffeine to restore spindle integrity in aging oocytes. We tested the effects of caffeine on the MII spindle with focus on microtubules and on the centrosome proteins gamma-tubulin and NuMA (nuclear mitotic apparatus protein). The results revealed that in porcine oocytes aged for 48 hr., centrosomes were absent and spindles became abnormal and disorganized; however, caffeine could prevent these changes or restore centrosome integrity in the meiotic spindle poles and displayed similar MII spindles as those seen in fresh oocytes.

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Section: Discussionmentioning

confidence: 90%

Centrosome abnormalities during porcine oocyte aging

Miao

Sun

Zhang

et al. 2009

Environ and Mol Mutagen

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“…A nimal cloning by somatic cell nuclear transfer (SCNT) has great potential applications in agriculture and regenerative medicine (Prather, 2007;Prather et al, 2003). Although mammalian cloning has been successfully developed over the last two decades (Wilmut et al, 1997), the success rate is low.…”

Section: Introductionmentioning

confidence: 99%

Oxamflatin Treatment Enhances Cloned Porcine Embryo Development and Nuclear Reprogramming

Mao

Zhao

Whitworth

et al. 2015

Cellular Reprogramming

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Faulty epigenetic reprogramming of somatic nuclei is thought to be the main reason for low cloning efficiency by somatic cell nuclear transfer (SCNT). Histone deacetylase inhibitors (HDACi), such as Scriptaid, improve developmental competence of SCNT embryos in several species. Another HDACi, Oxamflatin, is about 100 times more potent than Scriptaid in the ability to inhibit nuclear-specific HDACs. The present study determined the effects of Oxamflatin treatment on embryo development, DNA methylation, and gene expression. Oxamflatin treatment enhanced blastocyst formation of SCNT embryos in vitro. Embryo transfer produced more pigs born and fewer mummies from the Oxamflatin-treated group compared to the Scriptaid-treated positive control. Oxamflatin also decreased DNA methylation of POU5F1 regulatory elements and centromeric repeat elements in day-7 blastocysts. When compared to in vitro-fertilized (IVF) embryos, the methylation status of POU5F1, NANOG, and centromeric repeat was similar in the cloned embryos, indicating these genes were successfully reprogrammed. However, compared to the lack of methylation of XIST in day-7 IVF embryos, a higher methylation level in day-7 cloned embryos was observed, implying that X chromosomes were activated in day-7 IVF blastocysts, but were not fully activated in cloned embryos, i.e., reprogramming of XIST was delayed. A time-course analysis of XIST DNA methylation on day-13, -15, -17, and -19 in vivo embryos revealed that XIST methylation initiated at about day 13 and was not completed by day 19. The methylation of the XIST gene in day-19 control cloned embryos was delayed again when compared to in vivo embryos. However, methylation of XIST in Oxamflatin-treated embryos was comparable with in vivo embryos, which further demonstrated that Oxamflatin could accelerate the delayed reprogramming of XIST gene and thus might improve cloning efficiency.

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“…The gene in question codes for the protein hDAF (human decay-accelerating factor), one of the proteins that inhibits the so-called complement activation in humans (Siegert, Van Es, & Daha, 1996). Dysregulated coagulation in pig-to-primate xenotransplantation, reproduced with permission (Pierson III et al, 2009 Biotherapeutics to make an α-1,3-GalT knock-out of the Imutran pigs with an hDAF gene (Prather, 2007). Dysregulated coagulation in pig-to-primate xenotransplantation, reproduced with permission (Pierson III et al, 2009 Biotherapeutics to make an α-1,3-GalT knock-out of the Imutran pigs with an hDAF gene (Prather, 2007).…”

Section: 3) Cytos Biotechnology Is a Swiss Company Thatmentioning

confidence: 99%

“…Dysregulated coagulation in pig-to-primate xenotransplantation, reproduced with permission (Pierson III et al, 2009 Biotherapeutics to make an α-1,3-GalT knock-out of the Imutran pigs with an hDAF gene (Prather, 2007). One reason for this is that less than five percent of the islets of Langerhans in pigs have the Gal epitope, meaning that the risk of hyperacute rejection is smaller than in other pig organs (Prather, 2007). One reason for this is that less than five percent of the islets of Langerhans in pigs have the Gal epitope, meaning that the risk of hyperacute rejection is smaller than in other pig organs (Prather, 2007).…”

Section: 3) Cytos Biotechnology Is a Swiss Company Thatmentioning

confidence: 99%

Modern biotechnology

Tramper¹,

Zhu²

2011

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Targeted Genetic Modification: Xenotransplantation And Beyond

Cited by 10 publications

References 14 publications

Centrosome abnormalities during porcine oocyte aging

Centrosome abnormalities during porcine oocyte aging

Oxamflatin Treatment Enhances Cloned Porcine Embryo Development and Nuclear Reprogramming

Modern biotechnology

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