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SUPPRESSION BY CHLOROPHYLL, BUT PROMOTION BY CHLOROPHYLLIN, OF COLON CARCINOGENESIS IN THE FISHER 344 RAT

  • Blum, Carmen A.;Xu, Meirong;Orner, Gayle A.;Diaz, G.Dario;Li, Qingjie;Bailey, George S.;Dashwood, Roderick H.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.48-49
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    • 2001
  • The carcinogens 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) and 1, 2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnbl, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. In both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$_{33}$ in the rat tumors.(omitted)d)

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SUPPRESSION BY CHLOROPHYLL, BUT PROMOTION BY CHLOROPHYLLIN, OF COLON CARCINOGENESIS IN THE FISHER 344 RAT

  • Blum, Carmen A.;Xu, Meirong;Orner, Gayle A.;Diaz, G.Daria;Li, Qingjie;Bailey, George S.;Dashwood, Roderick H.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10b
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    • pp.5-6
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    • 2001
  • The carcinogens 2-arnioo-3-methylimidazo[4,5-f]quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the Fisher 344 rat that contain mutations in Ctnnb1, the gene for b-catenin, but the pattern of mutation differs from that found in human colon cancers. in both species, mutations affect the glycogen synthase kinase 3$\beta$ (GSK-3$\beta$) consensus region of $\beta$-catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser$^{33}$ in the rat tumors.(omitted)

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Utilizing cell-free DNA to validate targeted disruption of MYO7A in rhesus macaque pre-implantation embryos

  • Junghyun Ryu;Fernanda C. Burch;Emily Mishler;Martha Neuringer;Jon D. Hennebold;Carol Hanna
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.4
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    • pp.292-297
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    • 2022
  • Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.

Potential Prebiotic Properties of Whey Protein and Glycomacropeptide in Gut Microbiome

  • Bryna Rackerby;Hoang Ngoc M. Le;Avery Haymowicz;David C. Dallas;Si Hong Park
    • Food Science of Animal Resources
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    • v.44 no.2
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    • pp.299-308
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    • 2024
  • Proteins in whey have prebiotic and antimicrobial properties. Whey protein comprises numerous bioactive proteins and peptides, including glycomacropeptide (GMP), a hydrophilic casein peptide that separates with the whey fraction during cheese making. GMP has traditionally been used as a protein source for individuals with phenylketonuria and also has prebiotic (supporting the growth of Bifidobacterium and lactic acid bacteria) and antimicrobial activities. GMP supplementation may help positively modulate the gut microbiome, help treat dysbiosis-related gastrointestinal disorders and improve overall health in consumers.