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| COMPLETE HEPATIC REGENERATION AFTER SOMATIC DELETION OF AN ALBUMIN-PLASMINOGEN ACTIVATOR TRANSGENE |
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| Author(s): SANDGREN EP, PALMITER RD, HECKEL JL, DAUGHERTY CC, BRINSTER RL, DEGEN JL |
| Source: CELL Volume: 66 Issue: 2 Pages: 245-256 Published: JUL 26 1991 |
| Times Cited: 178 References: 46 |
| Abstract: We previously demonstrated that expression of an albumin-urokinase-type plasminogen activator (Alb-uPA) fusion construct in transgenic mice resulted in elevated plasma uPA concentration, hypofibrinogenemia, and neonatal hemorrhaging. Two lines of Alb-uPA mice were established in which only one half of the transgenic pups died at birth; surprisingly, plasma uPA concentrations in survivors gradually returned to normal by 2 months of age. The basis for this phenomenon is DNA rearrangement within hepatocytes that affects the transgene tandem array and abolishes transgene expression. Transgene-deficient cells selectively proliferate relative to surrounding liver, and this process culminates in replacement of the entire liver by clonal hepatic nodules derived from transgene-deficient progenitor cells. In some cases as few as two nodules can reconstitute over 90% of liver mass, highlighting the remarkable regenerative capacity of individual liver cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: SANDGREN, EP (reprint author), UNIV PENN, SCH VET MED, REPROD PHYSIOL LAB, PHILADELPHIA, PA 19104 USA |
Addresses:
1. UNIV WASHINGTON, HOWARD HUGHES MED INST, SEATTLE, WA 98195 USA
2. UNIV WASHINGTON, DEPT BIOCHEM, SEATTLE, WA 98195 USA
3. CHILDRENS HOSP RES FDN, CINCINNATI, OH 45229 USA
4. UNIV CINCINNATI, COLL MED, DEPT PEDIAT, CINCINNATI, OH 45229 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: FY712 |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |