Mouse Model for Cholangiocarcinoma from Peribiliary Glands

2018 ◽  
pp. 237-245 ◽  
Author(s):  
Hayato Nakagawa ◽  
Nobumi Suzuki ◽  
Kazuhiko Koike
Keyword(s):  
Mouse Model ◽  
Peribiliary Glands

scholarly journals Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands

2017 ◽  
Vol 114 (19) ◽  
pp. E3806-E3815 ◽  
Author(s):  
Hayato Nakagawa ◽  
Nobumi Suzuki ◽  
Yoshihiro Hirata ◽  
Yohko Hikiba ◽  
Yoku Hayakawa ◽  
...  
Keyword(s):  
Bile Duct ◽  
Mouse Model ◽  
Time Course ◽  
Extrahepatic Bile Duct ◽  
Genetic Alterations ◽  
Lineage Tracing ◽  
Cellular Origin ◽  
Regenerative Response ◽  
Peribiliary Glands ◽  
E Cadherin

The carcinogenic mechanism of extrahepatic cholangiocarcinoma (ECC) is unclear, due at least in part to the lack of an appropriate mouse model. Because human studies have reported frequent genetic alterations in the Ras- and TGFβ/SMAD-signaling pathways in ECC, mice with tamoxifen-inducible, duct-cell–specific Kras activation and a TGFβ receptor type 2 (TGFβR2) deletion were first generated by crossing LSL-KrasG12D, Tgfbr2flox/flox, and K19CreERT mice (KT-K19CreERT). However, KT-K19CreERT mice showed only mild hyperplasia of biliary epithelial cells (BECs) in the extrahepatic bile duct (EHBD) and died within 7 wk, probably a result of lung adenocarcinomas. Next, to analyze the additional effect of E-cadherin loss, KT-K19CreERT mice were crossed with CDH1flox/flox mice (KTC-K19CreERT). Surprisingly, KTC-K19CreERT mice exhibited a markedly thickened EHBD wall accompanied by a swollen gallbladder within 4 wk after tamoxifen administration. Histologically, invasive periductal infiltrating-type ECC with lymphatic metastasis was observed. Time-course analysis of EHBD revealed that recombined BECs lining the bile duct lumen detached due to E-cadherin loss, whereas recombined cells could survive in the peribiliary glands (PBGs), which are considered a BEC stem-cell niche. Detached dying BECs released high levels of IL-33, as determined by microarray analysis using biliary organoids, and stimulated inflammation and a regenerative response by PBGs, leading eventually to ECC development. Cell lineage tracing suggested PBGs as the cellular origin of ECC. IL-33 cooperated with Kras and TGFβR2 mutations in the development of ECC, and anti–IL-33 treatment suppressed ECC development significantly. Thus, this mouse model provided insight into the carcinogenic mechanisms, cellular origin, and potential therapeutic targets of ECC.

Regenerating myofibers in tibialis anterior muscles of young ‘MDX’ mice

1987 ◽  
Vol 45 ◽  
pp. 726-727
Author(s):  
H. D. Geissinge ◽  
L.D. Rhodes
Keyword(s):  
Muscular Dystrophy ◽  
Mouse Model ◽  
Tibialis Anterior ◽  
Physiological Activity ◽  
Mdx Mice ◽  
Mode Of Inheritance

A recently discovered mouse model (‘mdx’) for muscular dystrophy in man may be of considerable interest, since the disease in ‘mdx’ mice is inherited by the same mode of inheritance (X-linked) as the human Duchenne (DMD) muscular dystrophy. Unlike DMD, which results in a situation in which the continual muscle destruction cannot keep up with abortive regenerative attempts of the musculature, and the sufferers of the disease die early, the disease in ‘mdx’ mice appears to be transient, and the mice do not die as a result of it. In fact, it has been reported that the severely damaged Tibialis anterior (TA) muscles of ‘mdx’ mice seem to display exceptionally good regenerative powers at 4-6 weeks, so much so, that these muscles are able to regenerate spontaneously up to their previous levels of physiological activity.

Mouse model of gastric infection with cytotoxin-expressing strain of Helicobacter pylori in studying of pathogenesis of chronic gastric ulcer

1998 ◽  
Vol 13 (11-s4) ◽  
pp. S178-S184 ◽  
Author(s):  
PETER KONTUREK ◽  
TOMASZ BRZOZOWSKI ◽  
STANISLAW KONTUREK ◽  
ELZBIETA KARCZEWSKA ◽  
ROBERT PAJDO ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Ulcer ◽  
Mouse Model ◽  
Chronic Gastric Ulcer
Sign in / Sign up

Export Citation Format

Share Document