TY - JOUR
T1 - Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models
AU - Wahl, Lucas
AU - Karim, Arun
AU - Hassett, Amy R.
AU - van der Doe, Max
AU - Dijkhuizen, Stephanie
AU - Badura, Aleksandra
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024/11
Y1 - 2024/11
N2 - Background: Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a “behavioral fingerprint” that takes environmental and sex influences under consideration. Methods: To this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays—the Live Mouse Tracker and Motion Sequencing—on male and female Shank2, Tsc1, and Purkinje cell–specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. Results: Multiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. Conclusions: Together, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models.
AB - Background: Current phenotyping approaches for murine autism models often focus on one selected behavioral feature, making the translation onto a spectrum of autistic characteristics in humans challenging. Furthermore, sex and environmental factors are rarely considered. Here, we aimed to capture the full spectrum of behavioral manifestations in 3 autism mouse models to develop a “behavioral fingerprint” that takes environmental and sex influences under consideration. Methods: To this end, we employed a wide range of classical standardized behavioral tests and 2 multiparametric behavioral assays—the Live Mouse Tracker and Motion Sequencing—on male and female Shank2, Tsc1, and Purkinje cell–specific Tsc1 mutant mice raised in standard or enriched environments. Our aim was to integrate our high dimensional data into one single platform to classify differences in all experimental groups along dimensions with maximum discriminative power. Results: Multiparametric behavioral assays enabled a more accurate classification of experimental groups than classical tests, and dimensionality reduction analysis demonstrated significant additional gains in classification accuracy, highlighting the presence of sex, environmental, and genotype differences in our experimental groups. Conclusions: Together, our results provide a complete phenotypic description of all tested groups, suggesting that multiparametric assays can capture the entire spectrum of the heterogeneous phenotype in autism mouse models.
UR - http://www.scopus.com/inward/record.url?scp=85201576644&partnerID=8YFLogxK
U2 - 10.1016/j.bpsgos.2024.100366
DO - 10.1016/j.bpsgos.2024.100366
M3 - Article
AN - SCOPUS:85201576644
SN - 2667-1743
VL - 4
JO - Biological Psychiatry Global Open Science
JF - Biological Psychiatry Global Open Science
IS - 6
M1 - 100366
ER -