Journal of Inherited Metabolic Disease

, Volume 41, Issue 4, pp 669–677 | Cite as

MPS-IIIA mice acquire autistic behaviours with age

  • Adeline A. LauEmail author
  • Sarah J. Tamang
  • Kim M. Hemsley
Original Article


Mucopolysaccharidosis (MPS) type IIIA is an inherited, neurodegenerative lysosomal storage disorder resulting from mutations in the SGSH gene. Consequently, N-sulphoglucosamine sulphohydrolase enzyme activity is reduced resulting in impaired catabolism of heparan sulphate. After an asymptomatic period, patients typically show a progressive loss of cognitive and motor skills, with death often during the second decade of life. The diagnostic criteria of autism spectrum disorders (ASD) include impaired communication and social interactions, as well as displays of repetitive behaviours and fixed interests. Children with MPS-IIIA have been shown to exhibit decreased social communicative behaviours from approximately 3–4 years of age but behavioural stereotypies are mostly absent. In this study, we investigated whether a mouse model of MPS-IIIA exhibited ASD-like symptoms. The BTBR T+Itpr3tf/J inbred mouse model of autism was used as a positive control. Male MPS-IIIA and BTBR mice were less sociable compared with unaffected C57BL/6 male mice in the reciprocal social approach test administered at 20 weeks of age. Alternations in the frequency of social interactions was not evident at earlier stages of the disease course, suggesting an acquisition of ASD-like social behaviours. Stereotypical behaviours were not evident in male MPS-IIIA mice in the marble-burying test nor was the quality of nest constructed by mice affected. Collectively, these data suggest that MPS-IIIA mice acquire autistic social behaviours similar to the human condition, and thus they may be useful for elucidating symptom generating mechanisms and novel treatments for ASD.



Autism Diagnostic Observation Schedule


autism spectrum disorders


black and tan, brachyuric




N-sulphoglucosamine sulphohydrolase



This work was supported by the Hopwood Centre for Neurobiology (SAHMRI). We thank Roslyn Lau (Australian National University) for help implementing AVC, Autotyping and MatLab software; Meghan Setford for provision of some of the experimental and breeder animals; and Lynn Garrard and staff at the Women’s and Children’s Health Network for care of the mice.


This work was supported by the Hopwood Centre for Neurobiology (SAHMRI, Australia). The authors confirm that the content of the article has not been influenced by the sponsors.

Compliance with ethical standards

Conflict of interest

A. Lau, S. Tamang, and K. Hemsley declare that they have no conflict of interest.

Animal rights

All institutional and national guidelines for the care and use of laboratory animals were followed.

Informed consent

This article does not contain any studies with human subjects performed by any of the authors.

Supplementary material

10545_2018_160_Fig4_ESM.gif (18 kb)
Suppl. Fig. 1

Social contact in the reciprocal social approach test. Unfamiliar pairs of (a,c,e) male or (b,d,f) female mice of the same genotype were simultaneously introduced into the test chamber and video-taped for 10 minutes at various ages. Unique pairings were used at each time-point. Social interactions were then scored off-line without knowledge of sex/genotype for (a,b) upright rears facing towards each other or (c,d) vertical jump escape responses. No significant differences were found by ordinary ANOVA analyses (n=6-7 mouse pairs/group) (GIF 17 kb)

10545_2018_160_MOESM1_ESM.tif (4.4 mb)
High resolution image (TIFF 4466 kb)


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Copyright information

© SSIEM 2018

Authors and Affiliations

  1. 1.Childhood Dementia Research Group, Hopwood Centre for Neurobiology, Nutrition and Metabolism ThemeSouth Australian Health and Medical Research Institute (SAHMRI)AdelaideAustralia

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