JCB logo
MBL International Tel: 800.200.5459 CLICK HERE
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 19 December 2005. doi:10.1083/jcb.200507093
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 6, 931-937
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 6565K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nakamichi, I.
Right arrow Articles by Omary, M. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakamichi, I.
Right arrow Articles by Omary, M. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Report

 Keratin 8 overexpression promotes mouse Mallory body formation

Ikuo Nakamichi1,3, Diana M. Toivola1,3, Pavel Strnad1,3, Sara A. Michie2, Robert G. Oshima4, Hélène Baribault5, and M. Bishr Omary1,3

1 Department of Medicine, Stanford University, Palo Alto, CA 94305
2 Department of Pathology, Stanford University, Palo Alto, CA 94305
3 Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304
4 The Burnham Institute, La Jolla, CA 92037
5 Amgen, South San Francisco, CA 94080

Correspondence to Bishr Omary: mbishr{at}stanford.edu


Abstract
Keratins 8 and 18 (K8/18) are major constituents of Mallory bodies (MBs), which are hepatocyte cytoplasmic inclusions seen in several liver diseases. K18-null but not K8-null or heterozygous mice form MBs, which indicates that K8 is important for MB formation. Early stages in MB genesis include K8/18 hyperphosphorylation and overexpression. We used transgenic mice that overexpress K8, K18, or K8/18 to test the importance of K8 and/or K18 in MB formation. MBs were induced by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Livers of young K8 or K8/K18 overexpressors had no histological abnormalities despite increased keratin protein and phosphorylation. In aging mice, only K8-overexpressing livers spontaneously developed small "pre-MB" aggregates. Only K8-overexpressing young mice are highly susceptible to MB formation after short-term DDC feeding. Thus, the K8 to K18 ratio, rather than K8/18 overexpression by itself, plays an essential role in MB formation. K8 overexpression is sufficient to form pre-MB and primes animals to accumulate MBs upon DDC challenge, which may help explain MB formation in human liver diseases.

I. Nakamichi and D.M. Toivola contributed equally to this paper.

Abbreviations used in this paper: Ab, antibody; ALT, alanine aminotransferase; DDC, 3,5-diethoxycarbonyl-1,4-dihydrocollidine; IF, intermediate filament; MB, Mallory body; WT, wild type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents