mortality/aging
• on a CD-1-enriched genetic background, homozygotes die perinatally; however, survival can be extended up to P18 upon removal of wild-type littermates
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growth/size/body
• mutant tongues contain reduced interspersed adipose tissue
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• homozygotes display abnormal filiform papillae with reduced connective tissue
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• homozygotes show a reduction in the number of fungiform papillae
• those present at P12 appear disorganized and lack identifiable taste buds
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• homozygous mutant pups exhibit progressive wasting; postnatal survivors are only 30-35% the weight of wild-type littermates
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• homozygous mutant pups exhibit a 15% reduction in postnatal growth, despite normal birth weights
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vision/eye
• at E14.5-E18.5, homozygotes fail to form eyelids
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• homozygotes have open eyes at birth
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digestive/alimentary system
• mutant tongues contain reduced interspersed adipose tissue
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• homozygotes display abnormal filiform papillae with reduced connective tissue
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• homozygotes show a reduction in the number of fungiform papillae
• those present at P12 appear disorganized and lack identifiable taste buds
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• at P12 and P18, homozygotes display decreased BrdU labeling in the basal layer of the esophagus
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• although normal through P12, the mutant colonic epithelium displays an aberrant glandular architecture by P18
• at P18, tall disorganized branching crypt columns are occasionally found close to short rudimentary crypt columns
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liver/biliary system
• although normal at E17.5, mutant livers show aberrant sinusoidal anatomy and abnormal vacuolizatized nuclei by P8
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• by P8, mutant livers display thickened hepatocyte cords
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renal/urinary system
• homozygotes exhibit cystic dilation of collecting tubules, with a flattened instead of a cuboidal epithelial lining
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homeostasis/metabolism
• at P18, homozygotes display increased serum creatinine levels relative to wild-type littermates (2.4 mg/dl vs 0.1 mg/dl, respectively)
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• at P12, homozygotes display 75 mg/dl BUN vs 26 mg/dl in wild-type littermates; BUN reaches 288 mg/dl at P18
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nervous system
• after birth, homozygotes exhibit delayed migration of the EGC layer
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• at E18.5, homozygotes display a reduction in overall brain size; cortical regions are most affected
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• at E18.5, the mutant cerebral cortex appears relatively normal; however, neuroblast migration and cortical plate formation is impaired
• at E18.5, the mutant ventricular zone is thickened while the intermediate zone is markedly thinned in some mutants
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• by P18, homozygotes display atrophy of the anterior cerebral cortex, which is reduced to a thin sheet of cells
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• at E18.5, mutant olfactory bulbs appear normal in size and cell composition; however, by P14, mitral and tufted cells are nearly absent
• at P18, homozygotes show a shorter or absent molecular layer; in contrast, glomerular structures remain unaffected
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• at E18.5 and postnatally, the mutant cerebellar plate contains fewer Purkinje cells
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respiratory system
• at E18.5, 2 of 8 homozygotes show slightly immature lung histology and weaker surfactant staining possibly due to overall growth retardation
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craniofacial
• mutant tongues contain reduced interspersed adipose tissue
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• homozygotes display abnormal filiform papillae with reduced connective tissue
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• homozygotes show a reduction in the number of fungiform papillae
• those present at P12 appear disorganized and lack identifiable taste buds
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integument
• homozygotes have a fuzzy coat
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• homozygotes exhibit a delay in the appearance of emerging hair
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• by P5, the mutant hair shaft shows premature separation from the inner root sheath
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• by P2, homozygotes show a decline in interfollicular epidermal proliferation, reaching only 38% of the wild-type labeling index at P8
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• by P5, the mutant inner root sheath display premature hair keratinization and maturation
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• by P5, mutant hair follicles appear disoriented
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• by P5, mutant hair follicles are abnormally placed
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• mutant whiskers are fragile and appear to curl anteriorly
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• homozygous mutant pups display rudimentary waved whiskers
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