MPS-IIIA mice acquire autistic behaviours with age

Area of Science:

• Neurodegenerative Lysosomal Storage Disorders
• Autism Spectrum Disorders (ASD) Research
• Genetics of Inherited Diseases

Background:

• Mucopolysaccharidosis (MPS) type IIIA is a neurodegenerative lysosomal storage disorder caused by SGSH gene mutations, leading to impaired heparan sulfate metabolism.
• MPS type IIIA patients exhibit progressive cognitive and motor skill loss, with typical death in the second decade.
• While children with MPS-IIIA show social communication deficits, overt stereotypies are uncommon, unlike typical autism spectrum disorder (ASD) criteria.

Purpose of the Study:

• To investigate if a mouse model of MPS type IIIA exhibits autism spectrum disorder (ASD)-like symptoms.
• To compare the social behaviors of MPS type IIIA mice with a known autism mouse model (BTBR T+Itpr3tf/J) and wild-type controls.

Main Methods:

• Utilized male MPS type IIIA mice and BTBR T+Itpr3tf/J mice (positive control) alongside C57BL/6 mice (control).
• Assessed social behaviors using the reciprocal social approach test at 20 weeks of age.
• Evaluated stereotypical behaviors via the marble-burying test and assessed nest construction quality.

Main Results:

• Male MPS type IIIA mice and BTBR mice showed significantly reduced sociability compared to C57BL/6 mice.
• Social behavior alterations in MPS type IIIA mice appeared to be acquired, not present at earlier disease stages.
• No significant stereotypical behaviors were observed in MPS type IIIA mice in the marble-burying test, and nest construction quality was unaffected.

Conclusions:

• MPS type IIIA mice acquire autistic social behaviors comparable to the human condition.
• This mouse model may serve as a valuable tool for elucidating the mechanisms underlying ASD symptom generation.
• The MPS type IIIA mouse model offers potential for developing novel therapeutic strategies for ASD.