Analysis Tools
mortality/aging
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• homozygotes are born at near normal numbers but die within the first day after birth
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• homozygotes develop to term but die within 48 hrs of birth
• however, no obvious abnormalities are detected in the lungs, urogenital tract, skeleton, CNS, vasculature, pituitary, pancreas, liver, adrenals, or stomach
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growth/size/body
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• newborn homozygotes display an abnormal snout morphology with numerous ellipsoid epidermal protrusions instead of erupted vibrissae
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• at 3-12 hrs after birth, the body weight of homozygotes is ~20% lower than that of control littermates
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• at 3-12 hrs after birth, the crown-rump length of homozygotes is 12% shorter than that of control littermates
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homeostasis/metabolism
dehydration
(
J:87125
)
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• newborn homozygotes develop rapid and fatal dehydration immediately after birth
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• newborn homozygotes show extensive dye penetration across the entire epidermal surface, indicating a generalized loss of 'outwards in' epidermal barrier function that leads to dehydration
• in addition, homozygotes show an uncontrolled (5-fold faster) epithelial loss of fluids through evaporation at 37 C, indicating a severe loss of 'inwards out' epithelial barrier function
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immune system
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• newborn homozygotes exhibit widespread thymocyte apoptosis throughout the cortex and the medulla of the thymus, as revealed by TUNEL analysis
• flow cytometry analysis revealed a 5-fold increase in the apoptotic index and a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus
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• newborn homozygotes display a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus due to accelerated thymocyte apoptosis
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behavior/neurological
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• only 43% of newborn homozygotes followed up to 24 hrs after birth contain gastric milk spots, suggesting an inability to nurse properly
(J:87125)
• 75% of homozygous mutant pups lack milk spots in the stomach
(J:142708)
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craniofacial
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• newborn homozygotes display an abnormal snout morphology with numerous ellipsoid epidermal protrusions instead of erupted vibrissae
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hematopoietic system
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• newborn homozygotes exhibit widespread thymocyte apoptosis throughout the cortex and the medulla of the thymus, as revealed by TUNEL analysis
• flow cytometry analysis revealed a 5-fold increase in the apoptotic index and a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus
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• newborn homozygotes display a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus due to accelerated thymocyte apoptosis
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integument
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• newborn homozygotes show extensive dye penetration across the entire epidermal surface, indicating a generalized loss of 'outwards in' epidermal barrier function that leads to dehydration
• in addition, homozygotes show an uncontrolled (5-fold faster) epithelial loss of fluids through evaporation at 37 C, indicating a severe loss of 'inwards out' epithelial barrier function
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• mutant vibrissal hair shafts appear hypomorphic and are uniformly curved and ingrown
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• mutant pelage follicles are markedly hypoplastic, penetrate less deeply into the underlying dermis and overlying epidermis, and appear poorly differentiated
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• newborn homozygotes display hair canal agenesis
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• newborn homozygotes contain fewer pelage hair follicles than wild-type controls
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• newborn homozygotes show numerous aborted vibrissal follicle remnants in the nasal area, observed as large follicles in various stages of degeneration embedded in reactive hyperplastic epidermis
• mutant vibrissal follicles are abundant but severely hypomorphic; however, vascular sinuses, inner and outer root sheaths, follicular papillae, hair bulbs, and hair shafts are observed
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• all newborn homozygotes show absence of both erupted vibrissal hair shafts and vibrissal hair canals
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• all newborn homozygotes display striking malformations of the stratum corneum, including a less organized stratification
• only a few intercorneocyte lacunae are observed, resulting in an abnormally compact stratum corneum after H&E staining
• after glutaraldehyde fixation and toluidine blue staining, mutant corneocytes appear dysmorphic, pleiomorphic, and disorganized with a swollen, rather than flattened, appearance
• intracytoplasmic vesicular bodies are completely absent in transitional cells of the epidermis and in the extracellular space; absence of vesicular bodies is also noted in transitional cells within mutant hair follicles, suggesting a generalized defect in transitional cell function
• in contrast, the basal, spinous, and granular layers of the epidermis remain largely unaffected
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• after glutaraldehyde fixation and toluidine blue staining, mutant corneocytes appear dysmorphic, pleiomorphic, and disorganized with a swollen, rather than flattened, appearance
(J:87125)
• the stratum corneum is composed of tightly packed immature corneocytes
(J:142708)
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• newborn homozygotes exhibit an abnormally dry, wrinkled, red, and shiny skin on all body surfaces, including the trunk, limbs, tail, and face
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reddish skin
(
J:87125
)
shiny skin
(
J:87125
)
wrinkled skin
(
J:87125
)
cellular
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• newborn homozygotes exhibit widespread thymocyte apoptosis throughout the cortex and the medulla of the thymus, as revealed by TUNEL analysis
• flow cytometry analysis revealed a 5-fold increase in the apoptotic index and a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus
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endocrine/exocrine glands
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• newborn homozygotes exhibit widespread thymocyte apoptosis throughout the cortex and the medulla of the thymus, as revealed by TUNEL analysis
• flow cytometry analysis revealed a 5-fold increase in the apoptotic index and a ~50% reduction in the total number of immature CD4+CD8+ double positive T lymphocytes in the thymus
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