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Publication
Early motor phenotype detection in a female mouse model of Rett syndrome is
improved by cross-fostering.
Authors Vogel Ciernia A, Pride MC, Durbin-Johnson B, Noronha A, Chang A, Yasui DH,
Crawley JN, LaSalle JM
Submitted By Submitted Externally on 7/27/2017
Status Published
Journal Human molecular genetics
Year 2017
Date Published 5/1/2017
Volume : Pages 26 : 1839 - 1854
PubMed Reference 28334953
Abstract 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.




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