growth/size/body
• at P90, body weight is significantly lower than that of wild-type controls
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• growth begins to lag behind that of wild-type controls in the second month of life into adulthood
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digestive/alimentary system
• SEM analysis of the intestinal epithelium revealed bare regions that lack closely spaced villi
• villus surfaces appear rougher and less flat than those in wild-type controls
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• enterocytes exhibit a domed apical surface with an abnormal outward/convex curvature
• however, apical-basolateral polarity and simple columnar morphology remain normal
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• mean crypt depth at the proximal (duodenal) end of the small intestine is significantly decreased
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• TEM of the brush borders in jejunal tissues revealed that enterocytes show prominent apical doming
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• intermicrovillar adhesion complex (IMAC) components CDHR5, USH1C, and MYO7B are displaced from their normal localization at the tips of microvilli, unlike in wild-type controls
• microvilli are significantly shorter and more variable in length, and show a splayed morphology with significant physical separation and free space between neighboring protrusions
• intermicrovillar adhesion links, normally seen at the tips of wild-type microvilli, are almost entirely absent; in rare cases, remnant link-like structures between some microvilli are observed
• a subset of microvilli show irregular non-cylindrical shapes such that cross-sections show more angular or oblong profiles rather than circular and cross-sectional area is significantly increased
• misshapen microvilli have abnormally large, poorly consolidated core actin bundles or in some cases multiple core-like structures
• microvilli show a striking loss of hexagonal packing order and reduced packing density, with enterocytes having ~33% fewer protrusions per unit apical area relative to wild-type controls
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• mean villus length at the proximal (duodenal) end of the small intestine is significantly decreased
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• levels of key apical enzymes and transporters that are critical for enterocyte function are significantly reduced in the brush border
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endocrine/exocrine glands
• mean crypt depth at the proximal (duodenal) end of the small intestine is significantly decreased
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