| First Author | Nakamichi I | Year | 2005 |
| Journal | J Cell Biol | Volume | 171 |
| Issue | 6 | Pages | 931-7 |
| PubMed ID | 16365160 | Mgi Jnum | J:104502 |
| Mgi Id | MGI:3612202 | Doi | 10.1083/jcb.200507093 |
| Citation | Nakamichi I, et al. (2005) Keratin 8 overexpression promotes mouse Mallory body formation. J Cell Biol 171(6):931-7 |
| abstractText | 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. |
