UIC-2005-070 – Mouse model for mutant allele of the cell cycling inhibitor BARA in mice.

The invention is a research tool relating to the function of BARA(β-subunit Associated Regulator of Apoptosis)/LIN-9 downstream of CDK4 expression. BARA inhibits cell proliferation via collaboration with tumor suppressor Retinoblactoma protein (pRB). BARAΔ84/Δ84, the shortened version of BARA with the first 84 amino acids eliminated from the coding sequence of the gene, can be used in research of the cell cycle, growth hormone production, as well as cancer associated with pRB suppression. It has been proposed that C. elegans LIN-9 functions downstream of CDK4 in a pathway that regulates cell proliferation. At UIC the inventor found that mammalian BARA (β- subunit Associated Regulator of Apoptosis)/LIN-9 is a predominantly nuclear protein that inhibits cell proliferation. Furthermore, it was found that BARA/LIN-9 acts downstream of cyclin D/CDK4 in mammalian cells because its antiproliferative effect is partially blocked by coexpression of cyclin D1, and also because the mutant BARA form lacking the first 84 amino acids (BARAΔ84/Δ84) restores fertility, prevents onset of diabetes and reverses low mouse body size associated with mice null for cdk4. Notably, mutation of BARA/LIN-9 restores expression of the E2F target genes in CDK4 null MEFs, indicating that the wild-type protein plays a role in the expression of genes required for the G1/S transition. Veronica Haywood vhaywo2@uic.otm.edu 312-996-4865