Early motor phenotype detection in a female mouse model of Rett syndrome is improved by cross-fostering

Autor: Alene Chang, Annie Vogel Ciernia, Blythe Durbin-Johnson, Jacqueline N. Crawley, Adriana Noronha, Janine M. LaSalle, Dag H. Yasui, Michael C. Pride
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Methyl-CpG-Binding Protein 2
Physiology
Neurodegenerative
Medical and Health Sciences
Mice
Congenital
0302 clinical medicine
Neurodevelopmental disorder
Genotype
Cross-fostering
Genetics (clinical)
Motor skill
Mice
Knockout
Pediatric
Genetics & Heredity
Behavior
Animal
Articles
General Medicine
Biological Sciences
Phenotype
Mental Health
Motor Skills
Developmental Milestone
Female
congenital
hereditary
and neonatal diseases and abnormalities
Heterozygote
Offspring
Knockout
Intellectual and Developmental Disabilities (IDD)
Rett syndrome
Biology
Environment
Basic Behavioral and Social Science
MECP2
03 medical and health sciences
Rare Diseases
Behavioral and Social Science
medicine
Rett Syndrome
Genetics
Animals
Molecular Biology
Genetic Association Studies
Behavior
Animal
Neurosciences
medicine.disease
Brain Disorders
Disease Models
Animal
030104 developmental biology
Disease Models
030217 neurology & neurosurgery
Zdroj: Human molecular genetics, vol 26, iss 10
Popis: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the gene encoding methyl CpG binding protein 2 (MeCP2) that occur sporadically in 1:10,000 female births. RTT is characterized by a period of largely normal development followed by regression in language and motor skills at 6-18 months of age. Mecp2 mutant mice recapitulate many of the clinical features of RTT, but the majority of behavioral assessments have been conducted in male Mecp2 hemizygous null mice as offspring of heterozygous dams. Given that RTT patients are predominantly female, we conducted a systematic analysis of developmental milestones, sensory abilities, and motor deficits, following the longitudinal decline of function from early postnatal to adult ages in female Mecp2 heterozygotes of the conventional Bird line (Mecp2tm1.1bird-/+), as compared to their female wildtype littermate controls. Further, we assessed the impact of postnatal maternal environment on developmental milestones and behavioral phenotypes. Cross-fostering to CD1 dams accelerated several developmental milestones independent of genotype, and induced earlier onset of weight gain in adult female Mecp2tm1.1bird-/+ mice. Cross-fostering improved the sensitivity of a number of motor behaviors that resulted in observable deficits in Mecp2tm1.1bird-/+ mice at much earlier (6-7 weeks) ages than were previously reported (6-9 months). Our findings indicate that female Mecp2tm1.1bird-/+ mice recapitulate many of the motor aspects of RTT syndrome earlier than previously appreciated. In addition, rearing conditions may impact the phenotypic severity and improve the ability to detect genotype differences in female Mecp2 mutant mice.
Databáze: OpenAIRE
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