Distribution and frequency of intranuclear inclusions in female CGG KI mice modeling the fragile X premutation

Erik W. Schluter, Michael R. Hunsaker, Claudia M. Greco, Rob Willemsen, Robert F Berman

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the fragile X mental retardation 1 (FMR1) gene. The neuropathological hallmark of FXTAS is the presence of ubiquitin-positive intranuclear inclusions in neurons and in astroglia. Intranuclear inclusions have also been reported in the neurons of male CGG KI mice carrying an expanded CGG trinucleotide repeat and used to model FXTAS, but no study has been carried out quantifying inclusions in female CGG KI mice heterozygous for the fragile X premutation. We used histologic and immunocytochemical methods to determine the pathological features of intranuclear inclusions in astroglia and neurons. In female CGG KI mice, ubiquitin-positive intranuclear inclusions were found in neurons and astroglia throughout the brain in cortical and subcortical regions. These inclusions increased in number and became larger with advanced age and increasing CGG repeat length, supporting hypotheses that these pathologic features are progressive across the lifespan. The number of inclusions in neurons was reduced by ∼25% in female CGG KI mice compared to male CGG KI mice, but not so low as the 50% predicted. These data emphasize the need to evaluate the neurocognitive and pathological features in female carriers of the fragile X premutation with and without FXTAS symptomatology is warranted, as this population shows similar neuropathological features present in male FXTAS patients.

Original languageEnglish (US)
Pages (from-to)124-137
Number of pages14
JournalBrain Research
Volume1472
DOIs
StatePublished - Sep 7 2012

Fingerprint

Intranuclear Inclusion Bodies
Neurons
Trinucleotide Repeat Expansion
Astrocytes
Ubiquitin
Intellectual Disability
Neurodegenerative Diseases
Fragile X Tremor Ataxia Syndrome
Brain
Population
Genes

Keywords

  • CGG KI mouse
  • Fragile X premutation
  • Intranuclear inclusions
  • Trinucleotide repeat disorder

ASJC Scopus subject areas

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

Cite this

Distribution and frequency of intranuclear inclusions in female CGG KI mice modeling the fragile X premutation. / Schluter, Erik W.; Hunsaker, Michael R.; Greco, Claudia M.; Willemsen, Rob; Berman, Robert F.

In: Brain Research, Vol. 1472, 07.09.2012, p. 124-137.

Research output: Contribution to journalArticle

Schluter, Erik W. ; Hunsaker, Michael R. ; Greco, Claudia M. ; Willemsen, Rob ; Berman, Robert F. / Distribution and frequency of intranuclear inclusions in female CGG KI mice modeling the fragile X premutation. In: Brain Research. 2012 ; Vol. 1472. pp. 124-137.
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