Genetic and behavioral characterization of a Kmt2d mouse mutant, a new model for Kabuki Syndrome
| Autor: | Carlos Frederico Martins Menck, Sandra Regina Alexandre-Ribeiro, Pedro Kenzo Yamamoto, Ana Tada Fonseca Brasil Antiorio, Claudia Madalena Cabrera Mori, Silvia Maria Gomes Massironi, Nicassia de Souza Oliveira, Mariana de Souza Aranha Garcia-Gomes, Tiago Antonio de Souza, Dennis Albert Zanatto, Maria Martha Bernardi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Movement Mutant Biology medicine.disease_cause Mice 03 medical and health sciences Behavioral Neuroscience Chromosome 15 0302 clinical medicine Hearing Loss of Function Mutation Internal medicine Reflex Genetics medicine Animals Abnormalities Multiple ANIMAIS DE LABORATÓRIO Gait Mice Inbred BALB C Mutation Behavior Animal Histone-Lysine N-Methyltransferase medicine.disease Hematologic Diseases Hypotonia Motor coordination Disease Models Animal 030104 developmental biology Endocrinology Vestibular Diseases Neurology Face Muscle Hypotonia Righting reflex medicine.symptom Kabuki syndrome Myeloid-Lymphoid Leukemia Protein 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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 Thr1289 Ala 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. |
| Databáze: | OpenAIRE |
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