Analysis Tools
homeostasis/metabolism
| N |
• at 6 weeks of age, trans-epidermal water loss is normal, suggesting that the epithelial barrier is functional in mice free of cutaneous lesions
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• analysis of the electrophoretic pattern of type I collagen extracted from skin revealed that 50 to 80% of type I collagen still retains the aminopropeptide (pNalpha1I, pNalpha2I), similar to single Adamts2tm1Prc homozygotes
• in tendon, alpha chains represent ~75% of total type I collagen content, similar to single Adamts2tm1Prc homozygotes
• in cornea, alpha chains represent ~60% of total type I collagen content, similar to single Adamts2tm1Prc homozygotes
• in bone, only fully processed alpha 1 and alpha 2 chains are identified indicating normal type I procollagen processing, similar to single Adamts2tm1Prc homozygotes
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integument
| N |
• at 6 weeks of age, trans-epidermal water loss is normal, suggesting that the epithelial barrier is functional in mice free of cutaneous lesions
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• local induction of keratinocyte apoptosis leads to localized disruption of the epidermal barrier and onset of macroscopic epidermal lesions
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• proliferative index of the basal keratinocytes is increased only in affected skin regions
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dermatitis
(
J:271185
)
|
• double mutant mice develop an intrinsic atopic dermatitis-like syndrome due to immune dysregulation
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ruffled hair
(
J:271185
)
|
• at 3 weeks of age, double mutant mice exhibit a ruffled fur appearance, similar to that seen in single Adamts2tm1Prc homozygotes
|
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• in skin, the shape of collagen fibrils is highly heterogeneous and disrupted, ranging from fibrils with irregular contour to a ribbon-like structure, sometimes branched, similar to that in single Adamts2tm1Prc homozygotes
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• dermis is hypercellular around the skin lesions
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• increased dermis cellularity is due to immune cells infiltration and to higher fibroblastic density
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• epidermis becomes progressively thickened near lesions; however, epidermis is covered by abundant stratum corneum and contains a well-organized stratum granulosum
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• aging double mutant mice develop spontaneous epidermal lesions that worsen rapidly requiring euthanasia; such lesions are never observed in wild-type controls or single homozygotes
• epidermal lesions develop primarily in males (75% of males at >5 months of age) and affect back skin, ears, shoulders, snout and chin
• earliest lesions appear at 6 weeks of age; ~50% of double mutant mice have developed lesions by 3 months
• non-lesional skin shows presence of immune cells clusters, mainly T lymphocytes, in the dermis or in contact with the epidermis
• analysis of skin sections around the lesions indicates thickening of the epidermis, hypercellularity in the dermis and extensive infiltration by immune cells in the epidermis and the dermis
• blisters are never observed and the basement membrane at the dermo-epidermal junction is normal
• irradiated double mutant mice grafted with wild-type immune cells still develop lesions; epidermal rupture, keratinocytes hyperproliferation, infiltration of immune cells in the dermis and a high number of blood vessels are observed at the lesion site
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• when freshly excised skin strips are clamped into an Instron apparatus and stretched until rupture, reduction in tensile strength and % of elongation at rupture is similar to that in single Adamts2tm1Prc homozygotes
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immune system
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• a moderately increased number of mastocytes is observed only in affected skin regions
|
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• mice show a moderate decrease in blood B lymphocyte number and proportion at 8 weeks (asymptomatic) as well as at 10 and 12 weeks of age
• however, the total number of immune cells (CD45+) and percentages of T lymphocytes (CD3+), granulocytes (CD11b+CD46b-Gr1+) and monocytes (CD11b+CD49b-Gr1-) in blood are normal at all 3 time points
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• CD4+ T cell proportion is increased in blood at 10 and 12 weeks of age
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• CD8+ T cell proportion is decreased in blood at 10 and 12 weeks of age
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• CD4+ and CD8+ T cell activation is increased at 8 weeks of age
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• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen
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dermatitis
(
J:271185
)
|
• double mutant mice develop an intrinsic atopic dermatitis-like syndrome due to immune dysregulation
|
hematopoietic system
|
• a moderately increased number of mastocytes is observed only in affected skin regions
|
|
• mice show a moderate decrease in blood B lymphocyte number and proportion at 8 weeks (asymptomatic) as well as at 10 and 12 weeks of age
• however, the total number of immune cells (CD45+) and percentages of T lymphocytes (CD3+), granulocytes (CD11b+CD46b-Gr1+) and monocytes (CD11b+CD49b-Gr1-) in blood are normal at all 3 time points
|
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• CD4+ T cell proportion is increased in blood at 10 and 12 weeks of age
|
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• CD8+ T cell proportion is decreased in blood at 10 and 12 weeks of age
|
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• CD4+ and CD8+ T cell activation is increased at 8 weeks of age
|
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• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen
|
cellular
|
• local induction of keratinocyte apoptosis leads to localized disruption of the epidermal barrier and onset of macroscopic epidermal lesions
|
|
• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen
|
|
• proliferative index of the basal keratinocytes is increased only in affected skin regions
|
reproductive system
skeleton
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• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip, similar to those in single Adamts2tm1Prc homozygotes
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muscle
|
• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip, similar to those in single Adamts2tm1Prc homozygotes
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vision/eye
| N |
• despite an increased accumulation of pNalpha1I and pNalpha2I chains in the cornea, collagen fibers exhibit normal ultrastructure and organization
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