Molecular and pharmacological rescue of 16p11 Del phenotype with a MAPK/ERK inhibitor in mice

  • Awarded: 2013
  • Award Type: Research
  • Award #: 275316

One of the most common genetic causes of autism is the loss or duplication of a small region on human chromosome 16 known as 16p11.2. These genetic changes account for only about 1 percent of all cases of autism, but when present, they frequently result in the disorder.

There are only 27 genes in chromosomal region 16p11.2, giving researchers an opportunity to identify the genes responsible for the defects in brain development and the characteristic behavioral changes that typify autism.

Gary Landreth and his colleagues at Case Western Reserve University in Cleveland are using a new mouse model that mimics the loss of 16p11.2 to investigate which of the deleted genes lead to developmental defects in the brain.

They are focusing on two important genes — MAPK3 and MVP — that are responsible for transmitting signals from the outside of the cell to its interior, resulting in changes in cellular metabolism and gene expression. These genes are central components of the ERK MAP kinase pathway, mutations in which have been implicated in other neurological disorders.

Landreth’s preliminary findings indicate aberrant brain development and behavior in the mutant mice. He and his team plan to selectively remove the MAPK3 gene or the MVP gene, or both, to determine which is responsible for the altered brain development seen in autism. They also plan to test whether drugs that alter signaling in this pathway can be used to correct the impaired behavior observed in the mutant mice.

Subscribe to our newsletter and receive SFARI funding announcements and news