Reproducibility via coordinated standardization: a multi-center study in a Shank2 genetic rat model for Autism Spectrum Disorders

被引：18

作者：

Arroyo-Araujo, Maria ^{[1
]}

Graf, Radka ^{[2
]}

Maco, Martine ^{[3
]}

van Dam, Elsbeth ^{[4
]}

Schenker, Esther ^{[5
]}

Drinkenburg, Wilhelmus ^{[6
]}

Koopmans, Bastijn ^{[7
]}

de Boer, Sietse F. ^{[1
]}

Cullum-Doyle, Michaela ^{[2
]}

Noldus, Lucas P. J. J. ^{[4
]}

Loos, Maarten ^{[7
]}

van Dommelen, Wil ^{[4
]}

Spooren, Will ^{[2
]}

Biemans, Barbara ^{[3
]}

Buhl, Derek L. ^{[2
]}

Kas, Martien J. ^{[1
,8
]}

机构：

[1] Univ Groningen, Groningen Inst Evolutionary Life Sci, Groningen, Netherlands

[2] Pfizer Inc, Neurosci & Pain Res Unit, Cambridge, MA USA

[3] Roche Innovat Ctr Basel, Basel, Switzerland

[4] Noldus Informat Technol BV, Wageningen, Netherlands

[5] Inst Rech Servier, Croissy Sur Seine, France

[6] Janssen Pharmaceut NV, Janssen Res & Dev, Beerse, Belgium

[7] Syl Synaptol BV, Amsterdam, Netherlands

[8] Univ Med Ctr Utrecht, Dept Translat Neurosci, Utrecht, Netherlands

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

GLUTAMATE-RECEPTOR MGLUR1; BEHAVIOR; MICE; ADULT;

D O I：

10.1038/s41598-019-47981-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10