Genetic analyses of the Rb and p53 genes in murine development and tumorigenesis

The RB and p53 genes play central roles in cell cycle and checkpoint control, apoptosis and many other biological processes. These are central tumor suppressor genes that are each inactivated in many human cancers. Mouse genetic analyses have been used to dissect roles of these genes in development and cancer. Targeted disruption of the retinoblastoma gene in mice leads to embryonic lethality in midgestation accompanied by defective erythropoiesis. Rb-l- embryos also exhibit inappropriate cell cycle activity and apoptosis in the central nervous system (CNS), peripheral nervous system (PNS), and ocular lens. Loss of p53 can prevent the apoptosis in the CNS and lens; however, the specific signals leading to p53 activation have not been determined. We tested the hypothesis that hypoxia caused by defective erythropoiesis in Rb-null embryos contributes to p53-dependent apoptosis and found upregulation of hypoxia- inducible genes in CNS tissue from Rb-l- embryos. The Cre-loxP system was used to generate embryos in which Rb was deleted in the CNS, PNS and lens, in the presence of normal erythropoiesis.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• MacPherson, David (David P.)

Advisor dc:contributor.advisor

• Tyler Jacks.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/33752

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33752