Keratin 8 overexpression promotes mouse Mallory body formation

Ikuo Nakamichi, Diana M. Toivola, Pavel Strnad, Sara A. Michie, Robert G. Oshima, Hélène Baribault, M. Bishr Omary

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)931-937
Number of pages7
JournalJournal of Cell Biology
Volume171
Issue number6
DOIs
StatePublished - Dec 19 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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