Journal
JOURNAL OF IMMUNOLOGY
Volume 171, Issue 11, Pages 5787-5794Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.11.5787
Keywords
-
Categories
Funding
- NCI NIH HHS [CA76340] Funding Source: Medline
- NIDCD NIH HHS [5 T32 DC00026] Funding Source: Medline
- NIEHS NIH HHS [P30 ES06639] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA076340] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES006639] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [T32DC000026] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Her-2 transgenic (Tg) mice were generated with wild-type human c-ErbB-2 (Her-2) under the whey acidic protein promoter. They are tolerant to Her-2 and appropriate for testing Her-2 vaccines. The expression of transmembrane ErbB-2 from the whey acidic protein-Her-2 cassette and its up-regulation by insulin and hydrocortisone was verified by in vitro transfection. The transgene cassette was microinjected into fertilized eggs from B6C3 (C3H x C57BL/6) females mated with B6C3 males. Transgene-positive mice were backcrossed onto C57BL/6 mice. Human ErbB-2 was expressed in the secretory mammary epithelia during pregnancy and lactation and expressed constitutively in the Bergman glia cells within the molecular layer of the cerebellum. Overt, neoplastic transformation was not detected in any tissue examined. Tolerance to Her-2 was demonstrated by inoculating mice with a syngenic tumor expressing high levels of human ErbB-2. Tumors grew exclusively in Her-2 Tg mice without inducing an Ab response, while the nontransgenic littermates remained tumor free for 10 mo and mounted a robust anti-ErbB-2 Ab response. When immunized five times with plasmid DNA encoding secErbB-2 and GM-CSF, respectively, similar to33% of the Her-2 Tg mice rejected a lethal challenge of EL-4/E2 tumor cells, whereas all immunized littermates rejected the tumor. Therefore, Her-2 Tg mice express human ErbB-2 in the brain and mammary gland and demonstrated tolerance to ErbB-2 which was partially overcome by DNA vaccination. The breakable tolerance of Her-2 Tg mice resembles that in human and these mice are particularly suited for testing human ErbB-2 based vaccines.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available