On association of the lethal yellow (A Y) mutation in the agouti gene with the alterations in mouse brain and behavior

Behav Brain Res. 2019 Feb 1;359:446-456. doi: 10.1016/j.bbr.2018.11.013. Epub 2018 Nov 15.


Lethal yellow (AY) mutation causes obesity and type-2 diabetes in mice. Here we studied the effect of the AY mutation on the brain and behavior. The experiments were carried out on adult (11-12 weeks old) males of AY/a mice and their wild-type littermates (a/a). Mice of AY/a and a/a genotypes did not differ in their home cage activity, sleep, food and water consumption, learning ability in the Morris water maze, anxiety in the open field and elevated plus-maze, as well as in the level of monoamines, metabolites and some genes expression in the brain. At the same time, the fat mass, depressive-like immobility in the forced swim and tail suspension tests were significantly increased in AY/a mice compared with a/a ones. Magnetic resonance imaging revealed a significant reduction of cortex volume in AY/a mice. The level of mRNA of Ptpn5 gene encoding striatal enriched tyrosine phosphatase in the frontal cortex of AY/a mice was significantly elevated compared with their wild-type littermates. This is the first report on the alterations in the brain and behavior in the AY/a mouse line. It is tempting to speculate that this mouse line can serve as a new and useful preclinical model to study neurobehavioral complications associated with obesity and type-2 diabetes.

Keywords: Behavior; Brain; Lethal yellow; MRI; Mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti Signaling Protein / genetics*
  • Agouti Signaling Protein / metabolism
  • Animals
  • Behavior, Animal / physiology*
  • Body Composition / genetics
  • Body Composition / physiology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Genetic Association Studies
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Mutation*
  • Organ Size
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • RNA, Messenger / metabolism


  • Agouti Signaling Protein
  • RNA, Messenger
  • a protein, mouse
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Ptpn5 protein, mouse