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    자연과학 >생물ㆍ화학ㆍ환경 >생명공학
  • 등록일자
    2010.10.27
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    2,550
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We will study about transgenic mouse models, with emphasis on disease phenotypes in digestive and respiratory organs. In addition to regular classes, two students/each week will have meetings with a course director to get comments for references described in course syllabus.
Liver-Fas antibody-induced acute liver injury
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1. 비디오 Liver-Fas antibody-induced acute liver injury - Fas antigen is important in programmed cell death in the liver [Ogasawara J et al. Nature 364:806 (1993).]
- BH3-only proapoptotic protein, Bid, amplifies a weak death receptor signal in hepatocutes rendering the liver more sensitive to FasL-induced apoptosis [Schungel S et al. Hepatology 50:1558 (2009)].
URL
2. 비디오 Liver-acetaminophen-induced acute liver injury Acetaminophen (APAP) overdose leads to drug-induced liver damage.
- C-Jun N-terminal kinase (JNK) plays a major role to promote APAP-induced hepatotoxicity [Gunawan BK et al. Gastroenterology 131:165 (2006)].
- Deletion of apoptosis signal-regulating kinase 1 (ASK1) attenuates APAP-induced liver injury by inhibiting JNK. ASK1 likely is involved in the liver damage by prolongation of JNK activation [Nakagawa H et al. Gastroenterology 135:1311 (2008)].
URL
3. 비디오 Quizz about acute liver injury URL
4. 비디오 Liver-steatohepatitis - Loss of B-catenin in the liver leads to defective cholesterol and bile acid metabolism in the liver and increased susceptibility to developing steatohepatitis in the face of metabolic stress [Behari J et al. Am J Pathol 176:744 (2010)]. URL
5. 비디오 Liver-hemochromatosis - The C282Y mutation in the HFE gene explains 80–90% of all diagnosed cases of hereditary hemochromatosis (HH) that is characterized by iron accumulation, followed by organ damage. C294Y mice demonstrated significantly higher hepatic iron levels compared with wild-type mice. [Tomatsu S, et al, PNAS 100:15788 (2003)].
- Iron deposition predominantly in hepatocyes is associated with more severe liver damage in patients with NAFLD. However, there was no significant association between HFE mutations and the severity of liver fibrosis. [Valenti L et al. Gastroenterology 138:905 (2010)].
URL
6. 비디오 Quizz about liver-steatohepatitis, hemochromatosis URL
7. 비디오 Pancreas-a role of incretin receptor signaling in STZ-induced diabetes in mice - Differential importance of glucose-dependent insulinotropic polypeptide vs
glucagon-like peptide 1 receptor signaling for beta cell survival in mice [Maida A et al. Gastroenterology 137:2146 (2009)]
- There are functionally important differences in the pharmacologic and physiologic roles of incretin receptors in beta cells. GLP-1R signaling exerts more robust control of beta cell survival, relative to GIPR activation or dipeptidylpeptidase-4 inhibition in mice in vivo.
URL
8. 비디오 Pancreas-Hedgehog signaling in regeneration - Hedgehog Signaling Is Required for Effective Regeneration of Exocrine Pancreas [Fendrich V et al. Gastroenterology 135:621 (2008)]
- Using a model of cerulein-mediated injury and repair, this study demonstrates that mature exocrine cells actively contribute to regenerating pancreatic epithelium through formation of metaplastic ductal intermediates.
- Acinar cell regeneration is associated with
activation of Hedgehog (Hh) signaling.
URL
9. 비디오 Quizz about Pancreas-GIP/GLP1, Hedgehog URL
10. 비디오 Pancreas-Notch signaling in a mouse model of pancreatic ductal adenocarcinoma - Inhibition of r-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma [Plentz R et al. Gastroenterology 136:1741 (2009)]
- Expression of activated Kras (KrasGOF) in acinar cells leads to PanIN formation, which is accelerated in the presence of activated Notch.
- Loss of the tumor suppressor p53 (p53LOF) allows progression to invasive tumors, which can be repressed by blocking Notch signaling with a GSI.
URL
11. 비디오 Pancreas-Notch signaling in acinar-to-B-cell conversion - Notch signaling as gatekeeper of rat acinar-to-B-cell conversion in vitro [Baeyens L et al. Gastroenterology 136:1750 (2009)]
- Ductal metaplasia of cultured acinar cells can be directly induced by Notch, or indirectly (still requiring Notch function) by epidermal growth factor (EGF) receptor agonists.
- Cultured acinar cells can be efficiently forced to become functional B-cells, in the presence of EGF and leukemia inhibitory factor (LIF), by an initial activation of Notch (acinar-to-duct) followed by its inhibition (duct-to-B-cell).
URL
12. 비디오 Intestine-NOD2 null mice - Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract [Kobayashi KS et al. Science 307:731 (2005) ]
- Protective immunity mediated by Nod2
recognition of bacterial muramyl dipeptide is abolished in Nod2-deficient mice.
- These animals are susceptible to bacterial infection via the oral route but not through intravenous or peritoneal delivery.
- Nod2 is required for the expression
of a subgroup of intestinal anti-microbial peptides, known as cryptdins.
URL
13. 비디오 Intestine-NOD2 2939iC mice - Nod2 mutation in Crohn’s disease
potentiates NF-kB activity and IL-1b processing [Maeda S et al. Science 307:734 (2005)]
- NOD2 2939iC mice exhibited elevated NF-kB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1b (IL-1b).
- These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kB activation and IL-1b secretion.
URL
14. 비디오 Intestine-MyD88 null mice - Recognition of commensal microflora
by Toll-Like Receptors is required for intestinal homeostasis [Rakoff-Nahoum et al. Cell 118:229 (2004)]
- Severe susceptibility to colonic injury
in MyD88-deficient mice.
- TLR-mediated recognition of commensals in the colon regulates production of tissue protective factors.
- Commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis.
URL

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