bile-duct-ligation-mice-induction-inflammatory-liver-injury-fibrosis

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well ...

RWTH Aachen University

The latent transforming growth factor-beta (TGF-beta) binding protein-1 belongs to a family of matrix glycoproteins that is functionally associated with the assembly and secretion of TGF-beta. We have isolated and sequenced a murine approximately 15-kbp contig containing part of Ltbp-1 and used a mouse-hamster radiation hybrid panel to determine its chromosomal localization on distal mouse chromosome 17. This map location is syntenic to human chromosomal subband 2p21-22. Similarly, human LTBP-1 was mapped to 2p21-22 by fluorescence in situ hybridization. Like in humans, the murine Ltbp-1 gene directs the synthesis of two different transcript sizes encoding two alternatively spliced isoforms (Ltbp-1S and Ltbp-1L), which are regulated in a tissue-and stage-dependent manner. Sequence analysis and database searches further reveal that the upstream regions of both isoforms are devoid of TATA and CAAT boxes but contain other putative binding sites for several transcription factors conserved in mouse and human. The utilization of different promoters and their evolutionarily conservation further emphasize the complex regulation of Ltbp-1.

The murine latent transforming growth factor-beta binding protein (Ltbp-1) is alternatively spliced, and maps to a region syntenic to human chromosome 2p21-22.

The cysteine and glycine rich protein 2 (CRP2) encoded by the Csrp2 gene is a LIM domain protein expressed in the vascular system, particularly in smooth muscle cells. It exhibits a bimodal subcellular distribution, accumulating at actin-based filaments in the cytosol and in the nucleus. In order to analyze the function of CRP2 in vivo, we disrupted the Csrp2 gene in mice and analysed the resulting phenotype.

Targeted disruption of the mouse Csrp2 gene encoding the cysteine- and glycine-rich LIM domain protein CRP2 result in subtle alteration of cardiac ultrastructure.

Neuropsychiatric affection involving extrapyramidal symptoms is a frequent component of Wilson's disease (WD). WD is caused by a genetic defect of the copper (Cu) efflux pump ATPase7B. Mouse strains with natural or engineered transgenic defects of the Atp7b gene have served as model of WD. These show a gradual accumulation and concentration of Cu in liver, kidneys, and brain. However, still little is known about the regional distribution of Cu inside the brain, its influence on other metals and subsequent pathophysiological mechanisms. We have applied laser ablation inductively coupled plasma mass spectrometry and performed comparative metal bio-imaging in brain sections of wild type and Atp7b null mice in the age range of 11-24 months. Messenger RNA and protein expression of a panel of inflammatory markers were assessed using RT-PCR and Western blots of brain homogenates.

Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson's disease by laser ablation inductively coupled plasma mass spectrometry.

Sabine Weiskirchen

Institute of Molecular Pathobiochemistry,
Experimental Gene Therapy and Clinical Chemistry,
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry

RWTH Aachen University

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Sabine Weiskirchen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Institute of Molecular Pathobiochemistry,Experimental Gene Therapy and Clinical Chemistry,Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry

RWTH Aachen University

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Institute of Molecular Pathobiochemistry,
Experimental Gene Therapy and Clinical Chemistry,
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry