Analysis Tools
mortality/aging
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• 95-99% of homozygotes die within 2 weeks of birth due to chylous ascites and lymphatic dysfunction
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homeostasis/metabolism
skin edema
(
J:89618
)
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• newborn homozygotes display a clearly raised and translucent skin, indicating subcutaneous edema
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• rare homozygotes surviving to P25 often display severe clear or chylous ascites as well as signs of chronic lymph stasis throughout the body
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• by P2, more than 90% of mutant pups exhibit chylous ascites resulting from lymphatic vessel dysfunction
• upon initial feedings, the entire mutant peritoneum is filled with a milky triglyceride-rich fluid, which is also frequently found in the pleural cavity
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cardiovascular system
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• at P10, mutant retinas remain peripherally avascular, whereas wild-type retinas display a complex superficial network extending over the entire surface of the retina and branches forming the deeper vascular layers
• at best, a rudimentary superficial vascular plexus is found in the central retina of mutant eyes
• despite the absence of surface retinal vessels and their initial deep sprouts, the neural architecture of mutant retinas is histologically normal at P10
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• rare homozygotes surviving to P25 develop a secondary pathologic angiogenesis in which the aberrantly retained hyaloid vasculature becomes hyperplastic and invades the avascular retina noted at P10
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• homozygotes exhibit impaired postnatal vascular regression and sprouting in the retina
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vision/eye
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• at P10, mutant retinas remain peripherally avascular, whereas wild-type retinas display a complex superficial network extending over the entire surface of the retina and branches forming the deeper vascular layers
• at best, a rudimentary superficial vascular plexus is found in the central retina of mutant eyes
• despite the absence of surface retinal vessels and their initial deep sprouts, the neural architecture of mutant retinas is histologically normal at P10
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• rare homozygotes surviving to P25 develop a secondary pathologic angiogenesis in which the aberrantly retained hyaloid vasculature becomes hyperplastic and invades the avascular retina noted at P10
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• a well-developed hyaloid vasculature is abnormally retained in mutant eyes at P10, unlike in wild-type eyes where the hyaloid vasculature has largely regressed at this stage
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immune system
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• following injection of Evans blue dye in the hind paw, mutant lymphatic channels and lymph nodes fail to become filled with dye, idicating lymphatic dysfunction
• upon necropsy, large mesenteric lymphatic vessels from mutant pups are filled with white chyle and appear to be disorganized, lacy, and enveloped by a diffuse halo of chylous fluid, indicating leakage
• disorganized large mesenteric lymphatic vessels are often surrounded by poorly associated clusters of smooth muscle cells, indicating a defect in smooth muscle investiture
• small intestinal lymphatic vessels from mutant pups appear to be highly irregular and are occasionally sparse and much more dilated or absent from segments of intestine; also, the lymph vessels do not appear to be organized around the arterioles in the submucosa
• in ear skin, mutant lymphatic vessels form an irregular network, with channels of variable size, spacing, and orientation
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digestive/alimentary system
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• central lymphatic lacteals (major site of lipid uptake in the intestine) of mutant pups are frequently absent and, when present, are abnormally short, although villus blood vessels appear unaffected
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integument
skin edema
(
J:89618
)
|
• newborn homozygotes display a clearly raised and translucent skin, indicating subcutaneous edema
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respiratory system
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• upon initial feedings, a milky triglyceride-rich fluid is frequently found in the pleural cavity
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cellular
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• homozygotes exhibit impaired postnatal vascular regression and sprouting in the retina
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