TY - JOUR
T1 - Reproducibility via coordinated standardization
T2 - a multi-center study in a S hank2 genetic rat model for Autism Spectrum Disorders
AU - Arroyo-Araujo, María
AU - Graf, Radka
AU - Maco, Martine
AU - van Dam, Elsbeth
AU - Schenker, Esther
AU - Drinkenburg, Wilhelmus
AU - Koopmans, Bastijn
AU - de Boer, Sietse F.
AU - Cullum-Doyle, Michaela
AU - Noldus, Lucas P.J.J.
AU - Loos, Maarten
AU - van Dommelen, Wil
AU - Spooren, Will
AU - Biemans, Barbara
AU - Buhl, Derek L.
AU - Kas, Martien J.
PY - 2019/8/12
Y1 - 2019/8/12
N2 - Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders.
AB - Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders.
UR - http://www.scopus.com/inward/record.url?scp=85070719091&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-47981-0
DO - 10.1038/s41598-019-47981-0
M3 - Article
C2 - 31406134
AN - SCOPUS:85070719091
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11602
ER -