Copy number variants (CNVs) affecting a number of different chromosomal regions have been implicated in the development of autism and schizophrenia. One such region, 16p11.2, includes approximately 25 genes, including mitogen-activated protein kinase 3 (MAPK3), which plays a key role in the MAPK/ERK kinase cascade. MAPK3 is also associated with schizophrenia and/or autism in several GWAS studies. There is a single high-scoring ortholog is Drosophila, rolled (Dmel\rl), for which an extensive number of mutations, including classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\rl is also orthologous to the human gene MAPK1.
Several UAS constructs of the wild-type human Hsap\MAPK3 gene have been introduced into flies as part of a large-scale study of human synaptic genes.
In an RNAi-based screen of Drosophila genes orthologous to human genes within the 16p11.2 region, knockdown of Dmel\rl was observed to result in neuroanatomy defects in larval neuromuscular junctions, including multiple and ectopic innervations of presynaptic motor axons into postsynaptic body-wall muscles. A large number of physical and genetic interactions for Dmel\rl have been described; see below and in the rl gene report.
[updated Jun. 2019 by FlyBase; FBrf0222196]