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Characterizing enteric pathology in MPS IIIA mice suggests disease-specific vulnerability among lysosomal storage disorders
Ewa A. Ziółkowska, Letitia Williams, Elizabeth Eultgen, Grace R. Kick, Xukai Ding, Alexander Sorensen, Steven Le, Balraj Doray, Patricia I. Dickson, Robert O. Heuckeroth, Jonathan D. Cooper
Ewa A. Ziółkowska, Letitia Williams, Elizabeth Eultgen, Grace R. Kick, Xukai Ding, Alexander Sorensen, Steven Le, Balraj Doray, Patricia I. Dickson, Robert O. Heuckeroth, Jonathan D. Cooper
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Research Letter Gastroenterology Genetics Neuroscience

Characterizing enteric pathology in MPS IIIA mice suggests disease-specific vulnerability among lysosomal storage disorders

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Abstract

Authors

Ewa A. Ziółkowska, Letitia Williams, Elizabeth Eultgen, Grace R. Kick, Xukai Ding, Alexander Sorensen, Steven Le, Balraj Doray, Patricia I. Dickson, Robert O. Heuckeroth, Jonathan D. Cooper

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Figure 1

Lack of severe enteric phenotypes in disease endstage MPS IIIA mice.

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Lack of severe enteric phenotypes in disease endstage MPS IIIA mice.
(A)...
(A) SGSH enzyme activity in WT mice is higher in all bowel regions versus brain. (B) No significant difference in overall bowel length (pylorus to anus) between genotypes. (C–E) H&E-stained jejunal sections show normal bowel architecture with intact villi, crypts, and smooth muscle in both genotypes, with no significant difference when quantified. (F) HuC/D-immunostained myenteric plexus reveals well-preserved ganglion organization. (G) HuC/D+ neuron densities were statistically equivalent in duodenum and colon, with a small but significant reduction in ileum neuron density in Sgsh–/– mice. (H) Ileum of Sgsh–/– mice also shows significantly fewer S100B+ but not GFAP+ enteric glia. (I and J) Carmine red (n = 12 mice/group) and FITC–dextran assays (n = 13 mice/group) revealed similar whole bowel transit and segmental distribution. Scale bars: 200 μm (C, F, and H). Data are shown as mean ± SEM (B, D, E, and G–I), using unpaired 2-tailed t test. *P < 0.05, **P < 0.01.

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