title: The developmental pattern of the RAS/RAF/Erk1/2 pathway in the BTBR autism mouse model.
abstract: BTBR mice exhibit several autistic-like behaviors and are currently used as a model for understanding mechanisms that may be responsible for the pathogenesis of autism. Ras/Raf/ERK1/2 signaling has been suggested to play an important role in neural development, learning, memory, and cognition. Two studies reported that a deletion of a locus on chromosome 16 containing the mitogen-activated protein kinase 3 (MAPK3) gene, which encodes ERK1, is associated with autism. In the present study, Ras/Raf/ERK1/2 signaling was found to be up-regulated in BTBR mice relative to matched control B6 mice, to further suggest involvement in the pathogenesis of autism. To further characterize the developmental pattern of Ras/Raf/ERK1/2 signaling, varying stages during development were sampled to reveal an up-regulation in newborn and 2-week old BTBR mice relative to age-matched B6 mice. By the age of 3-week, Ras/Raf/ERK1/2 signaling in the brain of BTBR mice was unaltered relative to B6 mice, with this trend maintained in 6-week samples. These results suggest that the alteration of Ras/Raf/ERK signaling in the early developmental stages in mice could contribute to the noted autistic phenotype. Furthermore, these findings support the value of BTBR mice to serve as a human analog for autistic etiological research and aid in a better understanding of the developmental mechanisms of autism.
authors.affiliation: Department of Obstetrics & Gynecology, Nanfang Hospital, Guangzhou, China; Southern Medical University, Guangzhou, China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Yin
authors.affiliation: Department of Obstetrics & Gynecology, Nanfang Hospital, Guangzhou, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics & Gynecology, Nanfang Hospital, Guangzhou, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Jia
authors.affiliation: Department of Obstetrics & Gynecology, Nanfang Hospital, Guangzhou, China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Song
authors.affiliation: Southern Medical University, Guangzhou, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Natural Sciences, LarGuardia CC, CUNY, NY, NY 11101, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Alberts
authors.affiliation: Department of Obstetrics & Gynecology, Nanfang Hospital, Guangzhou, China. Electronic address: drmzhong@gmail.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000150:complications* / Q000235:genetics; D002658:Developmental Disabilities / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice
keywords: Autism; Autism mouse model; BTBR mice; Ras/Raf/Erk 1/2 signaling; Synapse