MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background.

Clementina Cobolli Gigli,Linda Scaramuzza,Charlotte Kilstrup-Nielsen,Nicoletta Landsberger,Francesco Bedogni,Marina Gabaglio,Elisa Bellini,Daniela Parolaro,Anna Gandaglia,Maurizio D'Esposito

doi:10.1371/journal.pone.0153473

Abstract

MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.1Bird strain probably represents the most used, enabled to disclose much of the roles of Mecp2. However, small litters with little viability and poor maternal care hamper the maintenance of the colony, thus limiting research on such animals. For this reason, past studies often used Mecp2 mouse models on mixed genetic backgrounds, thus opening questions on whether modifier genes could be responsible for at least part of the described effects. To verify this possibility, and facilitate the maintenance of the Mecp2 colony, we transferred the Mecp2tm1.1Bird allele on the stronger CD1 background. The CD1 strain is easier to maintain and largely recapitulates the phenotypes already described in Mecp2-null mice. We believe that this mouse model will foster the research on RTT.

Highlights

Mutations in the X-linked MECP2 gene cause a large spectrum of neurological disorders affecting almost 1 of 4000 individuals worldwide
C57BL/6 heterozygous Mecp2tm1.1Bird females were crossed with CD1 wt male mice (Crl:CD1 (ICR); Charles River) and the progeny backcrossed for 10 generations
In accordance with previous observations made on the B6 Mecp2-null model [34], we demonstrate a significant up-regulation of Hif1α transcription in the CD1 null cortex (Fig 8A)

Summary

Introduction

Mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2) cause a large spectrum of neurological disorders affecting almost 1 of 4000 individuals worldwide. Rett syndrome (RTT) was the first identified and certainly the most thoroughly characterized MECP2related disease [1,2]. RTT is a devastating genetic disorder that affects primarily young girls and represents the most common genetic cause of severe intellectual disability in females. RTT is usually characterized by a severe regression phase occurring between 12 and 18 months of age that leads to the loss of most, if not all, the previously acquired skills. Clinical symptoms include impaired cognitive and motor abilities, communication dysfunctions, breathing abnormalities, seizures, social withdrawal, hypotonia, scoliosis and stereotypic hand movements.

Methods

Results

Conclusion