scholarly journals DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Simona Hankeova ◽  
Jakub Salplachta ◽  
Tomas Zikmund ◽  
Michaela Kavkova ◽  
Noémi Van Hul ◽  
...  
Keyword(s):  
Bile Duct ◽  
Mouse Model ◽  
Mouse Models ◽  
New Technology ◽  
Intrahepatic Bile Duct ◽  
Alagille Syndrome ◽  
3D Analysis ◽  
Wild Type ◽  
Organ Function ◽  
Proof Of Principle

Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.

scholarly journals Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome

Development ◽  
2010 ◽  
Vol 137 (23) ◽  
pp. 4061-4072 ◽  
Author(s):  
J. J. Hofmann ◽  
A. C. Zovein ◽  
H. Koh ◽  
F. Radtke ◽  
G. Weinmaster ◽  
...  
Keyword(s):  
Bile Duct ◽  
Portal Vein ◽  
Intrahepatic Bile Duct ◽  
Alagille Syndrome ◽  
Duct Development

Knockout of histidine decarboxylase decreases bile duct ligation-induced biliary hyperplasia via downregulation of the histidine decarboxylase/VEGF axis through PKA-ERK1/2 signaling

2014 ◽  
Vol 307 (8) ◽  
pp. G813-G823 ◽  
Author(s):  
Allyson Graf ◽  
Fanyin Meng ◽  
Laura Hargrove ◽  
Lindsey Kennedy ◽  
Yuyan Han ◽  
...  
Keyword(s):  
Bile Duct ◽  
Protein Expression ◽  
Histidine Decarboxylase ◽  
Intrahepatic Bile Duct ◽  
Cytokeratin 19 ◽  
Wild Type ◽  
Histamine Secretion ◽  
Duct Ligation ◽  
Hematoxylin And Eosin

Histidine is converted to histamine by histidine decarboxylase (HDC). We have shown that cholangiocytes 1) express HDC, 2) secrete histamine, and 3) proliferate after histamine treatment via ERK1/2 signaling. In bile duct-ligated (BDL) rodents, there is enhanced biliary hyperplasia, HDC expression, and histamine secretion. This studied aimed to demonstrate that knockdown of HDC inhibits biliary proliferation via downregulation of PKA/ERK1/2 signaling. HDC−/− mice and matching wild-type (WT) were subjected to sham or BDL. After 1 wk, serum, liver blocks, and cholangiocytes were collected. Immunohistochemistry was performed for 1) hematoxylin and eosin, 2) intrahepatic bile duct mass (IBDM) by cytokeratin-19, and 3) HDC biliary expression. We measured serum and cholangiocyte histamine levels by enzyme immunoassay. In total liver or cholangiocytes, we studied: 1) HDC and VEGF/HIF-1α expression and 2) PCNA and PKA/ERK1/2 protein expression. In vitro, cholangiocytes were stably transfected with shRNA-HDC plasmids (or control). After transfection we evaluated pPKA, pERK1/2, and cholangiocyte proliferation by immunoblots and MTT assay. In BDL HDC−/− mice, there was decreased IBDM, PCNA, VEGF, and HDC expression compared with BDL WT mice. Histamine levels were decreased in BDL HDC−/−. BDL HDC−/− livers were void of necrosis and inflammation compared with BDL WT. PKA/ERK1/2 protein expression (increased in WT BDL) was lower in BDL HDC−/− cholangiocytes. In vitro, knockdown of HDC decreased proliferation and protein expression of PKA/ERK1/2 compared with control. In conclusion, loss of HDC decreases BDL-induced biliary mass and VEGF/HIF-1α expression via PKA/ERK1/2 signaling. Our data suggest that HDC is a key regulator of biliary proliferation.

scholarly journals A Mouse Model for Studying Post-Acute Arthritis of Chikungunya

2021 ◽  
Vol 9 (9) ◽  
pp. 1998
Author(s):  
Aileen Y. Chang ◽  
Sarah R. Tritsch ◽  
Abigail J. Porzucek ◽  
Arnold M. Schwartz ◽  
Margaux Seyler-Schmidt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Targeted Therapies ◽  
Scoring System ◽  
Chikungunya Virus ◽  
Evidence Based ◽  
Novel Therapies ◽  
Wild Type ◽  
Chikv Infection ◽  
Acute Arthritis

Chikungunya virus (CHIKV) was introduced to the Americas in 2013, causing two million infections across over thirty countries. CHIKV causes a chronic debilitating arthritis in one fourth of infected individuals and currently evidence-based targeted therapies for the treatment of CHIKV arthritis are lacking. Multiple mouse models of chikungunya have been developed to study acute CHIKV infection. In humans, post-CHIKV arthritis may persist for months to years after viremia from a CHIKV infection has resolved. Therefore, the development of a mouse model of post-acute arthritis of chikungunya may facilitate the study of potential novel therapeutics for this arthritis. In this article we describe the development of a wild-type immunocompetent C57BL/6 mouse model for post-acute arthritis of chikungunya, including a histologic inflammation scoring system, as well as suggestions for how this mouse model may be used to examine the efficacy of novel therapies for CHIKV arthritis.

A new mouse model of sclerosing cholangitis combining toxic and immune mediated bile duct injury

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
F Glaser ◽  
B Engel ◽  
C John ◽  
T Krech ◽  
A Carambia ◽  
...  
Keyword(s):  
Bile Duct ◽  
Mouse Model ◽  
Bile Duct Injury ◽  
Sclerosing Cholangitis ◽  
Immune Mediated

Localized Intrahepatic Bile Duct Dilatation without a Visible Mass or Stone as depicted on CT Images: Findings of Malignancy Prediction

2008 ◽  
Vol 59 (3) ◽  
pp. 163
Author(s):  
Ju Wan Choi ◽  
Gab Chul Kim ◽  
Han Young Jeong ◽  
Hui Joong Lee ◽  
Jae Hyuck Lee ◽  
...  
Keyword(s):  
Bile Duct ◽  
Intrahepatic Bile Duct ◽  
Ct Images ◽  
Bile Duct Dilatation ◽  
Duct Dilatation

[18F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9

2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
New Drugs ◽  
Imaging Data ◽  
Wild Type ◽  
Preclinical Research ◽  
Standardized Uptake Values ◽  
Pet Ct

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.

Sign in / Sign up

Export Citation Format

Share Document