Correcting deregulated Fxyd1 expression ameliorates a behavioral impairment in a mouse model of Rett syndrome

Valerie Matagne, Sarojini Budden, Sergio R. Ojeda, Jacob Raber

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2. Several genes have been shown to be MECP2 targets. We previously identified FXYD1 (encoding phospholemman; a protein containing the motif phenylalanine-X-tyrosine-aspartate), a gene encoding a transmembrane modulator of the Na, K-ATPase (NKA) enzyme, as one of them. In the absence of MECP2, FXYD1 expression is increased in the frontal cortex (FC) of both RTT patients and Mecp2Bird null mice. Here, we show that Fxyd1 mRNA levels are also increased in the FC and hippocampus (HC) of male mice carrying a truncating mutation of the Mecp2 gene (Mecp2308). To test the hypothesis that some of the behavioral phenotypes seen in these Mecp2 mutants could be ameliorated by genetically preventing the Fxyd1 response to MECP2 deficiency, we crossed Fxyd1 null male mice with Mecp2308 heterozygous females and behaviorally tested the adult male offspring. Mecp2308 mice had impaired HC-dependent novel location recognition, and this impairment was rescued by deletion of both Fxyd1 alleles. No other behavioral or sensorimotor impairments were rescued. These results indicate that reducing FXYD1 levels improves a specific cognitive impairment in MECP2-deficient mice.

Original languageEnglish (US)
Pages (from-to)104-114
Number of pages11
JournalBrain research
StatePublished - Feb 16 2013


  • Fxyd1
  • Learning and memory
  • Mecp2
  • Mouse model
  • Novel object location
  • Novel object recognition
  • Rett syndrome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


Dive into the research topics of 'Correcting deregulated Fxyd1 expression ameliorates a behavioral impairment in a mouse model of Rett syndrome'. Together they form a unique fingerprint.

Cite this