Phenotypic characterization and central nervous system analysis of mutant mice equilíbrio and mergulhador induced with the chemical mutagen ethylnitrosourea

• Grant number: 16/03180-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2016
• End date: December 31, 2017
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Claudia Madalena Cabrera Mori
• Grantee: Marianna Manes
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The recessive mutation mergulhador ("diver"; symbol - mlh), which was originated from an ENU mutagenesis program, severely affects the swimming abilities of affected mice when put in a water tank. Under normal conditions, mlh/mlh mice exhibit head tilting but show no other behavioral abnormalities such as circling or head tossing. The locus for mlh is on chromosome 5 (Chr 5) and was identified as an allele of the mutation tilted (tlt) that affects otoconial morphogenesis without causing collateral deafness. Tilted and mergulhador are then two alleles at the Otopetrin 1 (Otop1) locus. The other recessive mutant mice called equilibrium (eqlb) presents balance impairment and incoordination. Histopathology showed abnormal formation of cell layers of the cerebellum, with disorganization of Purkinje cells and thickening of the external granular layer. Genetic mapping has identified a mutation in the NADPH oxidase 3 gene (NOX3), chromosome 17, described in the literature as responsible for vestibular defects and the formation of otoconia. The aim of this research project is to perform the behavioral phenotyping, as well as the morphological and molecular characterization of the mutant mice equilibrio and mergulhador, seeking to establish animal models for the study of vestibular dysfunction in humans. Twenty 8-wk-old male equilibrio and mergulhador mice and their BALB/c controls will be used. Initially, tests were conducted in the open field and ordered by parameter evaluated in the following sequence: 1) general activity of animals and sensory system: vocal tremor, irritability, ear reflex, clamping the tail, corneal reflex and response to touch; 2) psychomotor tests: contortion, hindquarters, righting reflex, body tone and strength to grip; 3) evaluation of the central and autonomic nervous systems, tremors, convulsions, tail standing sedation, anesthesia, ataxia, ptosis, lacrimation, urination and defecation. The other tests we are using will be: object recognition tests, the behavior at elevated cross maze, the T-maze, motor coordination on high beam, behavioral response in the tail suspension test and in the forced swim test. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MANES, MARIANNA; ARANHA GARCIA-GOMES, MARIANA DE SOUZA; SANDINI, THAISA MEIRA; ZACCARELLI-MAGALHAES, JULIA; FLORIO, JORGE CAMILO; ALEXANDRE-RIBEIRO, SANDRA REGINA; WADT, DANILO; BERNARDI, MARIA MARTHA; GOMES MASSIRONI, SILVIA MARIA; CABRERA MORI, CLAUDIA MADALENA. Behavioral and neurochemical characterization of the mlh mutant mice lacking otoconia. Behavioural Brain Research, v. 359, p. 958-966, FEB 1 2019. (16/03180-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MANES, Marianna. Phenotypical characterization and central nervous system analysis of mutants equilíbrio and mergulhador induced by mutagenic agent n-ethyl-n-nitrosourea. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.