Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice.
The methyl-CpG binding protein 2 (Mecp2) gene encodes a nuclear transcriptional modulator highly expressed in post-mitotic neurons. Mutations of this gene cause a large spectrum of neurological disorders in humans. Several lines of mice harboring a constitutional deletion of Mecp2 are available. The use of these models is crucial to understand the basis of Mecp2-related pathologies. However, most of the studies performed using these lines focused on different postnatal time points. The aim of the present study was to provide a more complete description of the behavioral phenotype of the Mecp2(tm1.1Bird) mice. To this aim, we used a modified version of the SHIRPA protocol and a set of sensorimotor tests and respiratory metabolism measurements, in a longitudinal study of the Mecp2-null male mice (Mecp2(-/y)) from three weeks (weaning) to eight weeks of age. Our data document, for the first time, the sequential appearance of the in vivo deficits in this mouse line. The observed deficits initially concern major parameters (such as body weight), and are followed by involuntary and sensitive defects (reflexes). Subsequently, motor functions and respiratory metabolism are severally impaired. A detailed description of these gradual defects may help to identify their neuronal origin and to elaborate novel therapeutic strategies.
Pratte
Michel
M
INSERM U910, Faculté de Médecine de La Timone, 27 Boulevard Jean Moulin, F-13385 Marseille Cedex 05, France. michel.pratte@univmed.fr
Panayotis
Nicolas
N
Ghata
Adeline
A
Villard
Laurent
L
Roux
Jean-Christophe
JC
D000704:Analysis of Variance; D000818:Animals; D018737:Hand Strength / Q000502:physiology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D018763:Muscle Fatigue / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics*; D010641:Phenotype; D012119:Respiration / Q000235:genetics*; D045442:Rotarod Performance Test; D018709:Statistics, Nonparametric
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2