Progressive spatial processing deficits in a mouse model of the fragile X premutation

Area of Science:

• Neuroscience
• Genetics
• Neurodegenerative Disorders

Background:

• Fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the FMR1 gene.
• A CGG KI mouse model was developed to study FXTAS progression, exhibiting water maze deficits at 52 weeks.

Purpose of the Study:

• To investigate spatial information processing deficits in the CGG KI mouse model of FXTAS at different ages.
• To determine the temporal sequence of spatial processing impairments in FXTAS.

Main Methods:

• CGG KI mice were subjected to behavioral tasks assessing metric and topological spatial processing.
• Performance was evaluated at 12, 24, and 48 weeks of age.

Main Results:

• At 12 and 24 weeks, CGG KI mice failed metric but not topological spatial tasks.
• By 48 weeks, CGG KI mice exhibited deficits in both metric and topological spatial processing.
• Spatial processing impairments appeared progressively with age.

Conclusions:

• Hippocampal-dependent spatial processing deficits may precede parietal cortex-dependent impairments in FXTAS.
• The CGG KI mouse model recapitulates key aspects of FXTAS neuropathology and behavioral deficits.
• Early-onset spatial processing alterations are a potential hallmark of FXTAS progression.