We conduct in-depth behavioral analysis of inbred and mutant mouse strains to develop genetic models of neurodegenerative and psychiatric diseases (e.g. Parkinson’s Disease, Amyotrophic Lateral Sclerosis, Schizophrenia, Autism Spectrum Disorders, anxiety and depression). We study motor and cognitive functions as well as social and emotional behaviors by using automated systems and ethologically based direct behavioral observations.
A careful and in-depth analysis of behavior is pivotal for the development of animal models of neurodegenerative and psychiatric diseases. This can be achieved through the use of sophisticated and possibly automated tests. Among the most used animal models, the mouse has gained great relevance because of the availability of genetically modified mouse lines that allow the study of the pathophysiological mechanisms of human diseases, both sporadic and familial.
Disorders like Alzheimer’s, Parkinson’s, and Huntington’s Diseases, Amyotrophic Lateral Sclerosis, Schizophrenia and Autism Spectrum Disorders require a wide range of phenotypical analysis to pinpoint various aspects of behavior that could reflect as faithfully as possible the human symptoms, especially if detected at the early stages. It is also important that these analyses are conducted on mice of both sexes since most of the above mentioned diseases occur with a different incidence in males and females.
We already investigated in details the behavioral phenotype of mouse lines important for the study of Parkinson’s disease (Marazziti et al., 2004; Marazziti et al., 2007; Mandillo et al., 2013) and cerebellar functions (Marazziti et al., 2013) and we largely contributed to EU-funded projects focused on the set-up, validation and optimization of standard operating procedures for the study of mouse mutant phenotypes (Brown et al., 2005; Mandillo et al., 2008; Simon et al., 2013; Mandillo et al., 2014). More recently we are evaluating specific behavioral aspects of mouse models of ALS (Garbugino et al, 2018; Golini et al., 2020) and Myotonic Dystrophy type 1.
- Telethon Grant Project 2019, #GGP19035 (2020-2022). Gene editing in Myotonic Dystrophy type 1: assessment of efficiency, safety and therapeutic effect of CTG-repeat deletion in a mouse model of disease. PI: G. Falcone
- Behavioral phenotyping and Standard Operating Procedures validation within the activities of the International Mouse Phenotyiping Consortium (IMPC)
- Analysis of welfare and behavior by using the home cage monitoring Digital Ventilated System DVC® (Aut. Min. Salute N° 892/2017-PR)
- Validation of potential drug targets for ALS therapy (Aut. Min. Salute N° 914/2016-PR)
- Effects of voluntary exercise in the SOD1*G93A low-copy ALS mouse model (Aut. Min. Salute N° 166/2015-PR)
- Golini E, Rigamonti M, Iannello F, De Rosa C, Scavizzi F, Raspa M, Mandillo S (2020). A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS. Frontiers in Neuroscience 14: 896. doi: 10.3389/fnins.2020.00896
- Garbugino L, Golini E, Giuliani A, Mandillo S (2018). Prolonged voluntary running negatively affects survival and disease prognosis of male SOD1G93A low-copy transgenic mice. Front. Behav. Neurosci. 12: 275. doi.org/10.3389/fnbeh.2018.00275
- Bitetti A, Mallory AC, Golini E, Carrieri C, Carreño Gutiérrez H, Perlas E, Pérez-Rico YA, Tocchini-Valentini GP, Enright AJ, Norton WHJ, Mandillo S, O’Carroll D, Shkumatava A (2018). MicroRNA degradation by a conserved target RNA regulates animal behavior. Nat Struct Mol Biol., 25:244-251. doi: 10.1038/s41594-018-0032-x
- Meehan TF et al. […], International Mouse Phenotyping Consortium (2017). Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium. Nature Genetics, 49(8):1231-1238. doi: 10.1038/ng.3901.
- Mandillo S, Heise I, Garbugino L, Tocchini-Valentini GP, Giuliani A, Wells S, Nolan PM (2014). Early motor deficits in mouse disease models are reliably uncovered using an automated home-cage wheel-running system: a cross-laboratory validation. Disease Models and Mechanisms. 7(3):397-407. doi: 10.1242/dmm.013946
- Mandillo S, Golini E, Marazziti D, Di Pietro C, Matteoni R, Tocchini-Valentini GP (2013). Mice lacking the Parkinson’s related GPR37/PAEL receptor show non-motor behavioral phenotypes: age and gender effect. Genes Brain Behav. 12(4):465-77. doi: 10.1111/gbb.12041.
- Mandillo S, Tucci V, Holter SM, Meziane H, Al Banchaabouchi M, Kallnik M, Lad HV, Nolan PM, Ouagazzal AM, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Parker A, Riet F, Schneider I, Marazziti D, Auwerx JH, Brown SD, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W (2008) Reliability, Robustness, and Reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiological Genomics, 34: 243-255. doi: 10.1152/physiolgenomics.90207.2008.
Programs & resources
- Project Telethon 2019 #GGP19035 Gene editing in Myotonic Dystrophy type 1: assessment of efficiency, safety and therapeutic effect of CTG-repeat deletion in a mouse model of disease. PI: G. Falcone (IBBC).
- International Mouse Phenotyping Consortium-IMPC (2012- ). “Building a truly comprehensive functional catalogue of a mammalian genome”. www.mousephenotype.org
- INFRAFRONTIER2020 (2017-2020). Towards enduring mouse resources and services advancing research into human health and disease. European Commission H2020.
- Research Grant of the Italian National Research Council-CNR (2012-2017). Project “Invecchiamento” (Ageing), Subproject 1-Molecular mechanisms of aging and neurodegeneration. WP1.8 Transgenic models of brain ageing and longevity.
- INFRAFRONTIER-I3 (2013-2016). Development of mouse mutant resources for functional analyses of human diseases-Enhancing the translation of research into innovation. European Commission FP7-Health.
- PhenoScale (2009-2011) “Large-scale, high-throughput automated systems for phenotyping mouse models of human disease”. European Commission funded program (FP7-Health) # 223263.
- EUMODIC (2007-2011) “The European Mouse Disease Clinic: a distributed phenoptyping resource for studying human disease”, European Commission funded program (FP6-LIFESCIHEALTH), # LSHG-CT-2006- 037188.
- EUMORPHIA (2003-2006) “Understanding human disease through mouse genetics”, European Commission funded program (FP5), # QLG2-CT-2002- 00930.
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Automated mouse cages help reveal subtle disease signs