Analysis Tools
craniofacial
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• homozygotes show absence of cusps in lower mandibular molars
• incisors appear relatively normal
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• 2 of 15 homozygotes display absence of a third lower molar on one side of the jaw
• in contrast, all teeth of the upper jaw appear normal
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• homozygotes exhibit maturational defects in the development of lower molars
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• mutant mandibular molars often fail to erupt completely from the gums
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mortality/aging
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• 30% of homozygotes die within the first 2 weeks due to acute intestinal malabsorption
• surviving homozygotes recover rapidly, are fertile, and appear generally healthy as adults
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growth/size/body
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• homozygotes show absence of cusps in lower mandibular molars
• incisors appear relatively normal
|
|
• 2 of 15 homozygotes display absence of a third lower molar on one side of the jaw
• in contrast, all teeth of the upper jaw appear normal
|
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• homozygotes exhibit maturational defects in the development of lower molars
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• mutant mandibular molars often fail to erupt completely from the gums
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digestive/alimentary system
steatorrhea
(
J:64018
)
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• all moribund homozygotes develop steatorrhea in the neonatal period
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• surviving homozygotes show a 23% reduction in the length of the intestinal tract relative to wild-type mice
• ~70% of survivors display varying degrees of intestinal distension, with enlarged and paddle-shaped villi
• at P8, sick homozygotes exhibit blood accumulation in the intestinal lumen, that is evident even macroscopically
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• homozygotes show a mild delay in intestinal development relative to wild-type mice
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• surviving homozygotes with enlarged intestines exhibit intestinal hyperplasia rather than dilation
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• the mutant intestinal mucosa is engorged with lipid-staining vesicles, resulting in abnormal villus morphology
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small cecum
(
J:64018
)
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• as early as E13.5, all homozygotes display a small cecum relative to wild-type mice
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• adult homozygotes display aberrant villus morphology, with enlarged and paddle-shaped villi in the duodenum
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• at P7-P8, homozygotes exhibit enlarged villi, hyperplastic crypt regions, and lipid retention in the tips of villi mucosa in the jejunum
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• at P8, homozytes display hyperplastic crypts in the mutant jejunum
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• in the adult duodenum, mutant villi are enlarged and paddle-shaped
• in the adult jejunum, mutant villi are enlarged
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• homozygotes exhibit sublingual glands and ducts of normal size but disrupted cellular architecture
• notably, maturation of mucous-secreting acinar cells is delayed, resulting in occasional expansion of a minor non-acinar cell population, and reduced levels of mucous glycoproteins in neonatal glands
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• mutant stomachs exhibit prolonged chyme retention, suggesting abnormal peristalsis at some level of the gut canal
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immune system
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• homozygotes show severely impaired homing of leukocytes into the spleen, Peyer's patches and intestinal villi, largely due to loss of expression of the mucosal homing coreceptor Madcam1 in specialized endothelial cells of the viscera
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• homozygotes exhibit an ~84% reduction in IgA-secreting plasma cells
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• homozygotes display a 30% reduction in CD4+ T cells in the small intestine; in contrast, intraepithelial CD8+ T cells remain unaffected
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• homozygotes exhibit a 4- to 10-fold increase in total WBC count in peripheral blood, although the proportion of different cell types remains normal
• apparently, leukocytosis results from aberrant leukocyte homing to secondary immune organs
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• complete loss of zone-specific metallophilic macrophages
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• mutant spleens show a pronounced reduction of mononuclear cells within the red pulp, largely due to macrophage death occurring in both the neonatal and adult period
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small spleen
(
J:64018
)
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• at birth, most homozygotes exhibit a significantly reduced spleen size relative to wild-type mice
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• mutant spleens develop poorly from birth, resulting in partial or complete atrophy
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• mutant spleens show a disproportionate reduction in the B cell zone, with intermingling of B and T cells in the boundry regions
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• mutant spleens lack a histologically identifiable follicular marginal zone, with complete loss of zone-specific metallophilic macrophages
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• mutant spleens exhibit fused periarterial lymphoid sheaths
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absent spleen
(
J:64018
)
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• ~36% of homozygotes exhibit asplenia as adults
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• adult homozygotes exhibit significantly fewer and smaller intestinal PPs, with only 0-4 PPs found along the antimesenteric surface of small intestines vs 6-11 found in wild-type
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• some adult homozygotes display expansion of the mesenteric lymph nodes and/or the B cell follicles of peripheral lymph nodes
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muscle
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• mutant stomachs exhibit prolonged chyme retention, suggesting abnormal peristalsis at some level of the gut canal
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respiratory system
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• homozygotes exhibit maturational defects in both tooth and salivary gland development, suggesting impaired oropharyngeal patterning
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hematopoietic system
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• homozygotes show severely impaired homing of leukocytes into the spleen, Peyer's patches and intestinal villi, largely due to loss of expression of the mucosal homing coreceptor Madcam1 in specialized endothelial cells of the viscera
|
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• homozygotes exhibit an ~84% reduction in IgA-secreting plasma cells
|
|
• homozygotes display a 30% reduction in CD4+ T cells in the small intestine; in contrast, intraepithelial CD8+ T cells remain unaffected
|
|
• homozygotes exhibit a 4- to 10-fold increase in total WBC count in peripheral blood, although the proportion of different cell types remains normal
• apparently, leukocytosis results from aberrant leukocyte homing to secondary immune organs
|
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• complete loss of zone-specific metallophilic macrophages
|
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• mutant spleens show a pronounced reduction of mononuclear cells within the red pulp, largely due to macrophage death occurring in both the neonatal and adult period
|
small spleen
(
J:64018
)
|
• at birth, most homozygotes exhibit a significantly reduced spleen size relative to wild-type mice
|
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• mutant spleens develop poorly from birth, resulting in partial or complete atrophy
|
|
• mutant spleens show a disproportionate reduction in the B cell zone, with intermingling of B and T cells in the boundry regions
|
|
• mutant spleens lack a histologically identifiable follicular marginal zone, with complete loss of zone-specific metallophilic macrophages
|
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• mutant spleens exhibit fused periarterial lymphoid sheaths
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absent spleen
(
J:64018
)
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• ~36% of homozygotes exhibit asplenia as adults
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homeostasis/metabolism
steatorrhea
(
J:64018
)
|
• all moribund homozygotes develop steatorrhea in the neonatal period
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• at P6-P9 (crisis period), homozygotes exhibit significantly reduced levels of total triglycerides in serum
• however, at P5 (pre-crisis) homozygotes show normal levels of triglycerides, cholesterol, and apolipoproteins AIV, B100 and B48 in mutant intestines
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skeleton
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• homozygotes show absence of cusps in lower mandibular molars
• incisors appear relatively normal
|
|
• 2 of 15 homozygotes display absence of a third lower molar on one side of the jaw
• in contrast, all teeth of the upper jaw appear normal
|
|
• homozygotes exhibit maturational defects in the development of lower molars
|
|
• mutant mandibular molars often fail to erupt completely from the gums
|
endocrine/exocrine glands
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• at P8, homozytes display hyperplastic crypts in the mutant jejunum
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• homozygotes exhibit sublingual glands and ducts of normal size but disrupted cellular architecture
• notably, maturation of mucous-secreting acinar cells is delayed, resulting in occasional expansion of a minor non-acinar cell population, and reduced levels of mucous glycoproteins in neonatal glands
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cellular
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• homozygotes show severely impaired homing of leukocytes into the spleen, Peyer's patches and intestinal villi, largely due to loss of expression of the mucosal homing coreceptor Madcam1 in specialized endothelial cells of the viscera
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