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

Autor(es):Mostrar menos -

Yamamoto, Pedro K. ^[1] ; de Souza, Tiago A. ^[2] ; Antiorio, Ana T. F. B. ^[1] ; Zanatto, Dennis A. ^[1] ; Garcia-Gomes, Mariana de Souza A. ^[1] ; Alexandre-Ribeiro, Sandra R. ^[3] ; Oliveira, Nicassia de Souza ^[1] ; Menck, Carlos F. M. ^[2] ; Bernardi, Maria M. ^[4] ; Massironi, Silvia M. G. ^{[3, 1]} ; Mori, Claudia M. C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Av Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[4] Univ Paulista, Grad Program Environm & Expt Pathol, S O Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GENES BRAIN AND BEHAVIOR; v. 18, n. 8 NOV 2019.
• Citações Web of Science: 0

Resumo

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 Thr(1289)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. (AU)

• Processo FAPESP: 17/21103-3 - Caracterização fenotípica e molecular de duas linhagens de camundongos mutantes que apresentam alterações motoras e sensoriais como potenciais modelos para estudo de doenças neurológicas
• Beneficiário: Claudia Madalena Cabrera Mori
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/23659-6 - Caracterização de uma nova mutação com perda de função do gene KMT2D em camundongos
• Beneficiário: Pedro Kenzo Yamamoto
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 12/25387-2 - Estabelecimento de uma facility de sequenciamento de nova geração como ferramenta de investigação em sistemas biológicos
• Beneficiário: Carlos Frederico Martins Menck
• Modalidade de apoio: Auxílio à Pesquisa - Regular