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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: GENES BRAIN AND BEHAVIOR; v. 18, n. 8 NOV 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/21103-3 - Phenotypic and molecular characterization of two mutant mice strains with motor and sensorial impairment as potential models for the study of neurological diseases
• Grantee: Claudia Madalena Cabrera Mori
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/23659-6 - Characterization of a new mutation with loss of function in the KMT2D gene in mice
• Grantee: Pedro Kenzo Yamamoto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/25387-2 - Establishment of a next generation sequencing facility as a tool for research in biological systems
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Regular Research Grants