The researchers said their findings suggest that drugs already being tested for cancer and Huntington's disease might be useful in restoring some memory capability to patients with Rubinstein-Taybi syndrome (RTS). RTS is a heritable disorder characterized by mental and growth retardation and skeletal abnormalities. In humans, RTS occurs in about one in 125,000 births. The researchers propose that their findings could lead to treatments for RTS and other memory disorders as well as a means of improving memory in otherwise healthy individuals.
Two groups of researchers independently studied mutant mice deficient in "CREB binding protein" (CBP), which is a common target in patients with RTS. CBP is so named because it binds a key gene-regulating protein called CREB that is important for many functions including memory in animals from mollusks to humans.
CBP is a particularly hard-working protein. It serves as a molecular scaffold that helps assemble the machinery of gene transcription known to be necessary for formation of long-term memories. And critically, CBP acts as an enzyme that transfers acetyl groups onto the histone proteins that are part of the chromatin enfolding DNA in the chromosomes. Such acetylation is a central process in remodeling the chromatin to prepare the chromosome for gene transcription.
In one paper, Eric Kandel and his colleagues studied a mutant mouse -- developed in another laboratory -- in which one of the two copies of the gene for CBP had been knocked out. Such "haploinsufficiency" is thought to be a good animal model for Rubinstein-Taybi syndrome, because it mimics many of the symptoms of the disease.