| First Author | Crawford DR | Year | 2006 |
| Journal | Am J Pathol | Volume | 169 |
| Issue | 1 | Pages | 223-32 |
| PubMed ID | 16816375 | Mgi Jnum | J:110171 |
| Mgi Id | MGI:3639541 | Doi | 10.2353/ajpath.2006.051284 |
| Citation | Crawford DR, et al. (2006) Separate Origins of Hepatitis B Virus Surface Antigen-Negative Foci and Hepatocellular Carcinomas in Transgenic HBsAg (alb/psx) Mice. Am J Pathol 169(1):223-32 |
| abstractText | We have examined the development and transgene expression in liver lesions of transgenic mice bearing the hepatitis B surface antigen (HBsAg) gene of hepatitis B virus under the control of the albumin promoter (alb/psx) to study liver regeneration and hepatocellular carcinoma (HCC) associated with hepatitis B virus infection. Storage of the HBsAg in the endoplasmic reticulum precedes loss of liver cells and regenerative hyperplastic nodules that do not express HBsAg. Histological analysis indicated that HBsAg-negative foci and nodules arose from liver progenitor cells in the portal zone and lacked mRNA expression. Genomic DNA from eight of nine HBsAg-negative laser capture-excised liver foci showed loss of part of the alb/psx gene, whereas no loss of the actin gene was observed. The alb/psx DNA was intact in adjacent HBsAg-positive tissue. Sequencing of polymerase chain reaction products suggested that alterations in the HBsAg transgene in HBsAg-negative foci occurred via large-scale deletions as opposed to single-site mutations. Southern blot analysis of HCC from 2-year-old transgenic HBsAg mice, however, revealed an intact alb/psx gene. Thus, HBsAg-negative progenitor cells with deletions in the transgene appear to be responsible for compensatory regeneration of the liver, whereas HCCs arise from clonal expansion of hepatocytes with intact alb/psx transgenes. |
