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 |
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| 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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