Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Osmon, Karlaina J.L.; Vyas, Meera; Woodley, Evan; Thompson, Patrick; Walia, Jagdeep S.

doi:10.3791/55491

Cited by 17 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different neurological diseases cause significant motor impairments, and they can induce the same changes in a particular behavioral measurement; the use a battery of behavioral tests can help to deal with this problem and to estimate the differences in the mutant and wild‐type phenotypes . All together, the sequence of behavioral tests could assess the phenotypic behavior when investigating the different outcomes from the animal model . Thus, the phenotypic screening aimed to characterize the motor, sensory and nervous system aspects in mutant bapa mice compared with BALB/cJ control mice.…”

Section: Discussionmentioning

confidence: 99%

“…OFT is useful for investigating motor impairment in animal models of neuromuscular diseases. The test is also used to assess anxiety‐like and exploratory behaviors in mice . The data showed an increased rearing frequency, distance traveled and average speed of bapa mice compared with the control group, denoting hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

“…The test is also used to assess anxiety-like and exploratory behaviors in mice. 43,44 The data showed an increased rearing frequency, distance traveled and average speed of bapa mice compared with the control group, denoting hyperactivity. By contrast, genetically modified Kmt2d+/ßGeo mice presented general open-field activity similar to their controls.…”

Section: Bjornsson Et Almentioning

confidence: 93%

“…42 All together, the sequence of behavioral tests could assess the phenotypic behavior when investigating the different outcomes from the animal model. 43 Thus, the phenotypic screening aimed to characterize the motor, sensory and nervous F I G U R E 6 Spatial parameters in the gait analyze test: right (A) and left (B) forelimb stride length, forelimb step length (C) and step width (D), right (E) and left (F) hindlimb stride length, forelimb step length (G) and step width (H), forelimb (I) and hindlimb (J) gait symmetry with the bapa mutant (n = 7 males and 7 females) and BALB/cJ (n = 7 males and 7 females) mice. The dotted line indicates spatial symmetry value of 0.5.…”

Section: Bjornsson Et Almentioning

confidence: 99%

“…The general activity in the OFT assesses locomotor and behavior activity levels of mice and can be correlated with the psychomotor system function. 43 OFT is useful for investigating motor impairment in animal models of neuromuscular diseases. The test is also used to assess anxiety-like and exploratory behaviors in mice.…”

Section: Bjornsson Et Almentioning

confidence: 99%

See 4 more Smart Citations

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Yamamoto

Souza

Antiorio

et al. 2019

Genes Brain and Behavior

View full text Add to dashboard Cite

The recessive mutant mice bate palmas (bapa) ‐ claps in Portuguese arose from N‐ethyl‐N‐nitrosourea mutagenesis. A single nucleotide, T > C, change in exon 13, leading to a Thr1289Ala substitution, was identified in the lysine (K)‐specific methyltransferase 2D gene (Kmt2d) located on chromosome 15. Mutations with a loss‐of‐function in the KMT2D gene on chromosome 12 in humans are responsible for Kabuki syndrome (KS). Phenotypic characterization of the bapa mutant was performed using a behavioral test battery to evaluate the parameters related to general activity, the sensory nervous system, the psychomotor system, and the autonomous nervous system, as well as to measure motor function and spatial memory. Relative to BALB/cJ mice, the bapa mutant showed sensory and psychomotor impairments, such as hypotonia denoted by a surface righting reflex impairment and hindquarter fall, and a reduction in the auricular reflex, suggesting hearing impairment. Additionally, the enhanced general activity showed by the increased rearing and grooming frequency, distance traveled and average speed possibly presupposes the presence of hyperactivity of bapa mice compared with the control group. A slight motor coordination dysfunction was showed in bapa mice, which had a longer crossing time on the balance beam compared with BALB/cJ controls. Male bapa mice also showed spatial gait pattern changes, such as a shorter stride length and shorter step length. In conclusion, the bapa mouse may be a valuable animal model to study the mechanisms involved in psychomotor and behavior impairments, such as hypotonia, fine motor coordination and hyperactivity linked to the Kmt2d mutation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Bjornsson Et Almentioning

confidence: 93%

Section: Bjornsson Et Almentioning

confidence: 99%

Section: Bjornsson Et Almentioning

confidence: 99%

See 3 more Smart Citations

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Yamamoto

Souza

Antiorio

et al. 2019

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia

Morini

Gao

Montgomery

et al. 2019

The American Journal of Human Genetics

View full text Add to dashboard Cite

Familial dysautonomia (FD) is a recessive neurodegenerative disease caused by a splice mutation in Elongator complex protein 1 (ELP1, also known as IKBKAP); this mutation leads to variable skipping of exon 20 and to a drastic reduction of ELP1 in the nervous system. Clinically, many of the debilitating aspects of the disease are related to a progressive loss of proprioception; this loss leads to severe gait ataxia, spinal deformities, and respiratory insufficiency due to neuromuscular incoordination. There is currently no effective treatment for FD, and the disease is ultimately fatal. The development of a drug that targets the underlying molecular defect provides hope that the drastic peripheral neurodegeneration characteristic of FD can be halted. We demonstrate herein that the FD mouse TgFD9;Ikbkap D20/flox recapitulates the proprioceptive impairment observed in individuals with FD, and we provide the in vivo evidence that postnatal correction, promoted by the small molecule kinetin, of the mutant ELP1 splicing can rescue neurological phenotypes in FD. Daily administration of kinetin starting at birth improves sensory-motor coordination and prevents the onset of spinal abnormalities by stopping the loss of proprioceptive neurons. These phenotypic improvements correlate with increased amounts of full-length ELP1 mRNA and protein in multiple tissues, including in the peripheral nervous system (PNS). Our results show that postnatal correction of the underlying ELP1 splicing defect can rescue devastating disease phenotypes and is therefore a viable therapeutic approach for persons with FD.

show abstract

Fluoxetine rescues rotarod motor deficits in Mecp2 heterozygous mouse model of Rett syndrome via brain serotonin

et al. 2020

View full text Add to dashboard Cite

Motor skill is a specific area of disability of Rett syndrome (RTT), a rare disorder occurring almost exclusively in girls, caused by loss-of-function mutations of the Xlinked methyl-CpG-binding protein2 (MECP2) gene, encoding the MECP2 protein, a member of the methyl-CpG-binding domain nuclear proteins family. Brain 5-HT, which is defective in RTT patients and Mecp2 mutant mice, regulates motor circuits and SSRIs enhance motor skill learning and plasticity.In the present study, we used heterozygous (Het) Mecp2 female and Mecp2-null male mice to investigate whether fluoxetine, a SSRI with pleiotropic effects on neuronal circuits, rescues motor coordination deficits. Repeated administration of 10 mg/kg fluoxetine fully rescued rotarod deficit in Mecp2 Het mice regardless of age, route of administration or pre-training to rotarod. The motor improvement was confirmed in the beam walking test while no effect was observed in the hanging-wire test, suggesting a preferential action of fluoxetine on motor coordination. Citalopram mimicked the effects of fluoxetine, while the inhibition of 5-HT synthesis abolished the fluoxetine-induced improvement of motor coordination. Mecp2 null mice, which responded poorly to fluoxetine in the rotarod, showed reduced 5-HT synthesis in the prefrontal cortex, hippocampus and striatum, and reduced efficacy of fluoxetine in raising extracellular 5-HT as compared to female mutants. No sex differences were observed in the ability of fluoxetine to desensitize 5-HT1A autoreceptors upon repeated administration. These findings indicate that fluoxetine rescues motor coordination in Mecp2 Het mice through its ability to enhance brain 5-HT and suggest that drugs enhancing 5-HT neurotransmission may have beneficial effects on motor symptoms of RTT.

show abstract

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Cited by 17 publications

References 15 publications

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome

ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia

Fluoxetine rescues rotarod motor deficits in Mecp2 heterozygous mouse model of Rett syndrome via brain serotonin

Contact Info

Product

Resources

About