Molecular Biology

20050619
Pajvani UB1, Trujillo ME, Combs TP, Iyengar P, Jelicks L, Roth KA, Kitsis RN, Scherer PE.
https://www.ncbi.nlm.nih.gov/pubmed/15965483

Researchers genetically modified mice to have a specific protein, FKBP, on the surface of fat cells. These mice grow up just like normal mice. However, upon administering an agent, at any time during their life, these mice lose almost all of their fat cells.

The protein FKBP does not normally dimerize, or join together in pairs, but can be caused to dimerize in the presence of FK1012.

Thus, the surface of the fat cells, having the FKBP protein, can be dismantled using the dimerizing agent FK1012-analog. When this happens, the mouse loses fat cells and becomes a very lean mouse. Mice with the inducible fat loss were given the name FAT-ATTAC mice.

• Cell death is a normal and desirable part of metabolism, to clear tissues of cells that have degenerated and are performing poorly. Caspases, are normally involved in the execution of cell death (apoptosis). Researchers modified the caspases to include the FKBP protein.
• After 2 weeks of administering the dimerizing agent, the blood stream showed near knockout levels of cell signaling proteins normally produced by fat cells, such as leptin and other adipokines.
• Compared to genetically modified mice used in previous studies, FAT-ATTAC mice can be better subjects for study because they start off disease free, because fat loss can be easily induced at any stage of development, and because they recover from the fat loss and become normal again.
• Life is largely made of proteins. For more energy efficient use of DNA, proteins are often made from subunits or domains. Caspase 8, like all Caspases, has subunits p10 and p20.

(UNDER CONSTRUCTION)

— Marcos Reyes 2019/07/15 02:56