Supermys are the result of single-nucleotide polymorphism

At the same time, their anxiety decreases, they stop being afraid of open and brightly lit places, and the developed fear reflexes (contextual fear memory) disappear in 7 days, which is comparable to the effect of psychotropic drugs. The work of McGirr et al. Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition accepted for publication in the journal Neuropsychopharmacology.

The scientists used a library of genomic DNA of male mice that were exposed to a strong mutagen. After studying the DNA of 7776 animals in one of the mice, the necessary mutation was found in the PDE4B (Y358C) gene, which leads to the fact that in the enzyme molecule in the position corresponding to the localization of this single nucleotide substitution, cysteine appeared in place of the amino acid tyrosine residue). The mutation made the enzyme less active, as a result of which the level of cAMP in cells where PDE4B is expressed increased compared to the norm. At the same time, in other parts of the brain, where another variant of PDE is synthesized, the level of the signaling molecule did not change. Then, with the help of a series of crosses, scientists managed to breed homozygous mutants – mice with identical mutant gene alleles in homologous chromosomes.

The same behavioral features were found in all mutant mice. They stopped preferring dark, enclosed spaces and boldly went out and explored brightly lit and open areas. Also, unlike ordinary mice, they did not show fear when they smelled the cat's urine and were prone to risk. 

However, the most impressive discovery was a significant increase in the intellectual abilities of mice. They easily remembered and could distinguish the mice they had already seen. They also showed good results in passing the Morris water maze. Similar high (compared to normal mice) results were shown in other experiments on memory and learning. 

Phosphodiesterases are enzymes involved in the regulation of signaling pathways by degradation of cyclic adenosine monophosphates – intracellular signaling molecules that trigger various processes in cells. It is believed that the altered activity of phosphodiesterase 4B may be associated with major mental illnesses: schizophrenia and bipolar disorder. Currently, scientists are trying to find a pharmacological analogue capable of inhibiting the action of phosphodiesterase 4B in the same way. If it is found, then, potentially, it can become a promising drug for the treatment of mental illnesses, including post-traumatic stress disorder.

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17.08.2015