Mucopolysaccharidosis IIIA

Mucopolysaccharidosis IIIA (MPS IIIA), also known as Sanfilippo syndrome A, is an autosomal recessive lysosomal storage disorder. The disease is characterized by severe and progressive loss of cognitive and motor functions, behavioral deficits and eventually death in the second decade of life, although the severity and progression of the disease varies widely. MPS IIIA is caused by mutations in the SGSH gene that result in deficiency of the N-sulfoglucosamine sulfohydrolase enzyme and subsequent accumulation of undegraded heparan sulfate, lysosomal enlargement as well as cellular and organ dysfunction.
MPS IIIA mice (JAX#003780) contain a spontaneous Sgsh mutation, resulting in an almost complete loss of N-sulfoglucosamine sulfohydrolase activity. Mice show typical pathological features of the Sanfilippo syndrome A:

  • Memory deficits
  • Social behavior deficits
  • Reduced activity
  • Increased body weight
  • Neuroinflammation
  • Lysosomal pathology

 

Figure 1: Behavioral  analyses of MPS IIIA mice compared to wildtype (WT) littermates in the Three Chamber social test and Barnes maze test. A: social approach in the social  interaction test and (B) time animals spent in the target quadrant during the probe trial of the Barnes maze test at the age of 30 weeks. A: Two-Way ANOVA with Bonferroni‘s post hoc test. B: E: One Sample t-test; significances label differences compared to 25% (dotted line); *p<0.05; **p<0.01; ***p<0.0001.

 

Figure 2: Histological analysis of MPSIIIA mice compared to WT littermates for neuroinflammation in the cortex.  A: Immunoreactive area (IR) in percent of GFAP labeling. Mean+SEM; unpaired t-test. ***p<0.001. B: Representative images of GFAP labeling in the cortex of MPSIIIA and WT animals at the age of 30 weeks.
Figure 3: Histological analysis of MPSIIIA mice compared to WT littermates for lysosomal/endosomal membrane alterations in the cortex.  A: Immunoreactive area (IR) in percent of LIMP2 labeling. Mean+SEM; unpaired t-test. ***p<0.001. B: Representative images of LIMP2 labeling in the cortex of MPSIIIA and WT animals at the age of 30 weeks.

 

QPS Neuropharmacology offers a custom tailored study design for this model and we are flexible to accommodate to your special interest. We would be happy to test your compounds in the MPSIIIA mouse model! The most common readouts are:

 

  • Body weight
  • Activity
  • Memory deficits
  • Social deficits
  • Neuroinflammation
  • Lysosomal pathology

 

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