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    자연과학 >생물ㆍ화학ㆍ환경 >생명공학
  • 강의학기
    2011년 1학기
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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.
introduction
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1. 비디오 introduction URL
2. 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
3. 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
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
6. 비디오 Liver-fibrosis-angiopoietin 1, angiotensin II Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis [Taura K et al. Gastroenterology 135:1729 (2008)].
Angiotensin II activates IkB Kinase Phosphorylation of RelA at Ser536 to
promote myofibroblast survival and liver fibrosis [Oakley F et al. Gastroenterology 136:2334 (2009)]
URL
7. 비디오 Liver-fibrosis-angiotensin II Hepatic fibrogenesis requires sympathetic neurotransmitters [Oben JA et al. Gut 53:438 (2004)]
HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote
hepatic fibrosis.
URL
8. 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
9. 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
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
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
15. 비디오 Intestine-TLR5 Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation [Rhee SH et al. PNAS 102:13610 (2005)]
Flagellin TLR5 response is restricted to the basolateral apect of colonic mucosa.
Flagellin exposure to the injured colonic mucosa induces in vivo activation of MEK1/2 in colonic mucosa.
Flagellin exposed to injured colonic mucosa significantly aggravates the clinical symptoms of colitis.
Flagellin exposure to injured colon causes apoptosis in colonic epithelium.
URL
16. 비디오 Intestine-EP2-PGE2 Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice [Sonoshita M et al. Nat Med 7:1048 (2001)]
Homozygous deletion of the gene encoding a cell-surface receptor of PGE2, EP2, causes decreases in number and size of intestinal polyps in ApcΔ716 mice (a mouse model for human familial adenomatous polyposis). This effect is similar to that of COX-2 gene disruption.
Prostaglandin E2 Promotes Colon
Cancer Cell Growth Through a Gs-Axin-b-Catenin Signaling Axis [Castellone MD et al. Science 310 :1504 (2005)]
PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)–coupled receptor,
EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein bg subunits and the direct association of the G protein as subunit with the regulator of G protein signaling (RGS) domain of axin.
URL
17. 비디오 Intestine-MUC2 Muc2-Deficient Mice Spontaneously Develop Colitis, Indicating That Muc2 Is Critical for Colonic Protection [Van der Sluis M et al Gastroenterology 131:117 (2006)]
Muc2 -/- mice showed clinical signs of colitis (as of 5 weeks), aggravating
as the mice aged. Microscopic analysis of the
colon of Muc2 / mice showed mucosal thickening, increased proliferation, and superficial erosions.
URL
18. 비디오 Lung-KRAS Wildtype Kras2 can inhibit lung carcinogenesis in mice [Zhang Z et al. Nat Genet 29:25 (2001)]
Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice.
Wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.
URL
19. 비디오 Lung-EGFR EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy [Paez JG et al. Science, 304::1497 (2004)]
To determine whether mutation of receptor tyrosine kinases plays a causal role in NSCLC, somatic genetic alterations were searched in a set of 119 primary NSCLC tumors.
Identified mutations were L858R in activation loop, G719S in P-loop and deletion mutants in exon 19.
L858R mutant EGFR is particularly sensitive to inhibition by gefitinib compared with the wild-type enzyme.
URL
20. 비디오 동물내의 질병발현 2011. 06. 14 URL
21. 비디오 동물내의 질병발현 URL

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