| First Author | Ludlow A | Year | 2005 |
| Journal | J Cell Mol Med | Volume | 9 |
| Issue | 2 | Pages | 421-37 |
| PubMed ID | 15963261 | Mgi Jnum | J:100142 |
| Mgi Id | MGI:3587140 | Doi | 10.1111/j.1582-4934.2005.tb00367.x |
| Citation | Ludlow A, et al. (2005) Characterization of integrin beta6 and thrombospondin-1 double-null mice. J Cell Mol Med 9(2):421-37 |
| abstractText | To identify overlapping and non-overlapping functions for TSP-1 and alphavbeta6, we crossed TSP-1-null and beta6-null mice and compared the phenotype of the double-null mice with those of wild-type and single-null mice. The double-null mice exhibited focal acute and organizing pneumonia that was more severe than the wild-type and single-null mice as well as a significantly higher incidence of inflammation in tissues other than the lung. The TSP-1-null and beta6-null mice exhibited a five to eight-fold increase in granulocyte recruitment to the lung three days after exposure to lipopolysaccharide. They also had abnormalities that were infrequently observed in the wild-type and single-null mice, including heart degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of the glandular of the stomach (2.8% in wild-type and 21.1% in double-null mice) and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females). Furthermore, the beta6-null and double-null mice displayed a significant elevation in benign and malignant cancers. Stomach papillomas, squamous cell carcinomas of the ear and stomach, and adenocarcinomas of the lungs, vagina/cervix and colon were observed with the highest frequency. These data demonstrate that TSP-1 and alphavbeta6 are involved in regulation of the immune system and epithelial homeostasis. They also indicate that alphavbeta6 functions as a tumor suppressor gene and that activation of TGFbeta by TSP-1 and alphavbeta6 contributes to normal tissue architecture and function. |
