low-cost-protocol-footprint-analysis-hanging-box-test-for-mice

Low-cost Protocol of Footprint Analysis and Hanging Box Test for Mice Applied the Chronic Restraint Stress

Gait disturbance is frequently observed in patients with movement disorders. In mouse models used for movement disorders, gait analysis is important ...

Jichi Medical University

Dystonia is a neurological disorder with involuntary and simultaneous contractions of agonist and antagonist muscles. Rapid-onset dystonia parkinsonism (RDP), one of the heredity forms of dystonia, is caused by mutations of Na,K-ATPase α3 subunit gene (ATP1A3). The abrupt onset of bulbar and limb symptoms of RDP are often triggered by physical and/or emotional stress. We reported previously that Atp1a3-deficient heterozygous mice showed higher locomotor activity and developed enhanced dystonia symptoms after kainate injection into the cerebellum, but not spontaneous movement disorder like RDP patients. Here we show that Atp1a3-deficient heterozygous mice exhibited shorter stride length at 4 weeks of age without stress and at later stages under chronic restraint stress loading. Shorter hanging time in the hanging box test was also observed after stress loading. Shorter stride length and hanging time may be relevant to certain phenotypes, such as gait abnormality, observed in RDP patients. Atp1a3 was widely expressed in the brain, including basal ganglia and cerebellum, and spinal cord of young mice, and the expression pattern was compatible with movement abnormalities under lack of one of alleles. Our results demonstrated the usefulness of Atp1a3-deficient heterozygous mice as an animal model of RDP and its potential use to explore the pathophysiology of movement abnormality in this disorder. 

Heterozygous mice deficient in Atp1a3 exhibit motor deficits by chronic restraint stress.

Despite high estimates of the heritability of aggressiveness, the genetic basis for individual differences in aggression remains unclear. Previously, we showed that the wild-derived mouse strain MSM/Ms (MSM) exhibits highly aggressive behaviors, and identified chromosome 15 (Chr 15) as the location of one of the genetic factors behind this escalated aggression by using a panel of consomic strains of MSM in a C57BL/6J (B6) background. To understand the genetic effect of Chr 15 derived from MSM in detail, this study examined the aggressive behavior of a Chr 15 consomic strain towards different types of opponent. Our results showed that both resident and intruder animals had to have the same MSM Chr 15 genotype in order for attack bites to increase and attack latency to be reduced, whereas there was an intruder effect of MSM Chr 15 on tail rattle behavior. To narrow down the region that contains the genetic loci involved in the aggression-eliciting effects on Chr 15, we established a panel of subconsomic strains of MSM Chr 15. Analysis of these strains suggested the existence of multiple genes that enhance and suppress aggressive behavior on Chr 15, and these loci interact in a complex way. Regression analysis successfully identified four genetic loci on Chr 15 that influence attack latency, and one genetic locus that partially elicits aggressive behaviors was narrowed down to a 4.1-Mbp region (from 68.40 Mb to 72.50 Mb) on Chr 15. 

Mapping of Genetic Factors That Elicit Intermale Aggressive Behavior on Mouse Chromosome 15: Intruder Effects and the Complex Genetic Basis.

Mouse ultrasonic vocalizations (USVs) are studied in many fields of science. However, various noise and varied USV patterns in observed signals make complete automatic analysis difficult. We improve several methods to reduce noise, detect USV calls and automatically cluster USV calls. After reduction of noise and detection of USV calls, we consider USV calls as functional data and characterize them as USV functions with B-spline basis functions. For discontinuous USV calls, breakpoints in the USV functions are defined using multiple knots in the construction of the B-spline basis functions, and a hierarchical method is used to cluster the USV functions by shape. We finally show the performance of the proposed methods with USV data recorded for laboratory mice.

Article	Year
Heterozygous mice deficient in Atp1a3 exhibit motor deficits by chronic restraint stress. Behavioural brain research\| PubMed ID: 24983657	2014
Mapping of Genetic Factors That Elicit Intermale Aggressive Behavior on Mouse Chromosome 15: Intruder Effects and the Complex Genetic Basis. PloS one\| PubMed ID: 26389588	2015
Functional clustering of mouse ultrasonic vocalization data. PloS one\| PubMed ID: 29742174	2018

Hiroki Sugimoto

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