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| TUMOR SPECTRUM ANALYSIS IN P53-MUTANT MICE |
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| Author(s): JACKS T, REMINGTON L, WILLIAMS BO, SCHMITT EM, HALACHMI S, BRONSON RT, WEINBERG RA |
| Source: CURRENT BIOLOGY Volume: 4 Issue: 1 Pages: 1-7 Published: JAN 1 1994 |
| Times Cited: 940 References: 36 |
| Abstract: Background: The p53 tumor suppressor gene is mutated in a large percentage of human malignancies, including tumors of the colon, breast, lung and brain. Individuals who inherit one mutant allele of p53 are susceptible to a wide range of tumor types. The gene encodes a transcriptional regulator that may function in the cellular response to DNA damage. The construction of mouse strains carrying germline mutations of p53 facilitates analysis of the function of p53 in normal cells and tumorigenesis. Results: In order to study the effects of p53 mutation in vivo, we have constructed a mouse strain carrying a germline disruption of the gene. This mutation removes approximately 40 % of the coding capacity of p53 and completely eliminates synthesis of p53 protein. As observed previously for a different germline mutation of p53, animals homozygous for this p53 deletion mutation are viable but highly predisposed to malignancy. Heterozygous animals also have an increased cancer risk, although the distribution of tumor types in these animals differs from that in homozygous mutants. In most cases, tumorigenesis in heterozygous animals is accompanied by loss of the wild-type p53 allele. Conclusion: We reaffirm that p53 function is not required for normal mouse development and conclude that p53 status can strongly influence tumor latency and tissue distribution. |
| Document Type: Article |
| Language: English |
| Reprint Address: JACKS, T (reprint author), MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA |
Addresses:
1. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA
2. DANA FARBER CANC INST, BOSTON, MA 02215 USA
3. TUFTS UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02111 USA
4. TUFTS UNIV, SCH VET MED, BOSTON, MA 02111 USA
5. MIT, WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA
6. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA |
| Publisher: CURRENT BIOLOGY LTD, 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: MY541 |
| ISSN: 0960-9822 |
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