Keratin 8 overexpression promotes mouse Mallory body formation

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Nakamichi I, Toivola DM, Strnad P, Michie SA, Oshima RG, Baribault H, Omary MB
Publisher: ROCKEFELLER UNIV PRESS
Publication year: 2005
Journal: Journal of Cell Biology
Journal acronym: J CELL BIOL
Volume number: 171
Issue number: 6
Start page: 931
End page: 937
Number of pages: 7
ISSN: 0021-9525


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.

Last updated on 2019-19-07 at 05:13