Analysis Tools
behavior/neurological
| N |
• homozygotes do not exhibit any obvious behavioral deficits relative to wild-type mice
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craniofacial
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• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
|
|
• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
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hematopoietic system
| N |
• homozygotes do not exhibit any significant differences in the number of red blood cells, hematocrit or hemoglobin relative to wild-type
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homeostasis/metabolism
| N |
• homozygotes do not exhibit any significant differences in the levels of albumin, globulin, electrolytes, sodium, and chloride or in the hepatic enzymes, ALT and AST relative to wild-type
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immune system
| N |
• homozygotes do not exhibit any significant differences in the number of white blood cells relative to wild-type
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|
• after UUO, obstructed kidneys from mutant mice show early tubular damage and enhanced infiltration of macrophages relative to wild-type
• at day 53, a significant portion of affected tissue is occupied by infiltrating mononuclear cells, frequently in the form of lymphoid follicles
• in contrast, no differences in the extent of interstitial fibrosis are observed between mutant and wild-type mice
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muscle
|
• in 3-month-old homozygotes, tail tendon collagen fibrils show highly irregular, ragged outlines in cross-section relative to wild-type
• mutant tail tendons exhibit giant fibrils (>660 nm) with multiple lateral fusions; in contrast wild-type tendons have collagen fibrils with an average diameter of ~200 nm
• notably, numerous thin fibrils (40-60 nm) are interspersed with giant fibrils
• abnormal collagen morphology is associated with a decrease in collagen-bound proteoglycans
• although the typical, 67-nm periodicity of type I collagen is preserved, numerous d bands contain no orthogonally arrayed proteoglycan granules
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renal/urinary system
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• at 4-14 days after UUO, mutant obstructed kidneys display enhanced apoptosis exclusively in tubular epithelial cells
• in contrast, the degree of apoptosis in interstitial cells remains unaffected
|
|
• after UUO, obstructed kidneys from mutant mice show early tubular damage and enhanced infiltration of macrophages relative to wild-type
• at day 53, a significant portion of affected tissue is occupied by infiltrating mononuclear cells, frequently in the form of lymphoid follicles
• in contrast, no differences in the extent of interstitial fibrosis are observed between mutant and wild-type mice
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|
• at 150 days after UUO, pressure-induced injury to wild-type kidneys results in a significant up-regulation of biglycan, decorin, fibrillin-1, and fibrillin-2 expression
• after 150 days, 33% of ligated kidneys from mutant mice exhibit cystic dilatations of Bowman's capsular space and an attenuated upregulation of fibrillin-1; no such changes are observed in ligated kidneys from wild-type mice
• neither cystic dilatations of Bowman's space nor tubular cysts or hemorrhages into the renal pelvis are noted in mutant obstructed kidneys up to 70 days
• in mutants, overexpression of biglycan appears to substitute for decorin with respect to regulation of fibrillin-1 expression
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• at 4-14 days after UUO, mutant obstructed kidneys display a moderate increase in cell proliferation in tubular epithelial cells
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• after unilateral ureteral obstruction (UUO), homozygotes exhibit marked changes in the course and outcome of tubulointerstitial fibrosis of the obstructed kidney relative to wild-type mice; these differences can be explained by specific effects of decorin on apoptosis via p27KIP1 signaling, TGF-beta activity, and collagen turnover
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• prior to unilateral ureteral obstruction (UUO), homozygotes show normal renal morphology and matrix deposition relative to wild-type mice
• after UUO, both wild-type and mutant mice develop hydronephrosis with no major differences in the size of the obstructed and contralateral kidneys up to 35 days
• thereafter, obstructed kidneys from homozygotes become progressively smaller in size and weight
• notably, serum urea and creatinine levels and urinary protein excretion remain unaffected
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• after UUO, end-stage kidneys from mutant mice appear more atrophic than wild-type kidneys as a result of enhanced degradation of type I collagen
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• at day 53 after UUO, tubules with segment-specific differentiation are no longer identifiable in mutant mice (tubular atrophy)
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• at day 7 after UUO, mutant obstructed kidneys display a higher percentage of dilated tubules relative to wild-type obstructed kidneys
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skeleton
| N |
• radiographically, homozygotes do not exhibit any overt bone defects relative to wild-type mice
|
|
• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
|
|
• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
|
|
• in 3-month-old homozygotes, tail tendon collagen fibrils show highly irregular, ragged outlines in cross-section relative to wild-type
• mutant tail tendons exhibit giant fibrils (>660 nm) with multiple lateral fusions; in contrast wild-type tendons have collagen fibrils with an average diameter of ~200 nm
• notably, numerous thin fibrils (40-60 nm) are interspersed with giant fibrils
• abnormal collagen morphology is associated with a decrease in collagen-bound proteoglycans
• although the typical, 67-nm periodicity of type I collagen is preserved, numerous d bands contain no orthogonally arrayed proteoglycan granules
|
vision/eye
| N |
• homozygotes show no significant differences in packing or average size of corneal collagen fibrils relative to wild-type
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integument
|
• in 3-month-old homozygotes, dermal collagen fibrils are coarser, less orderly packed, and irregular in size and shape relative to wild-type
• in mutant dermis, large (>200 nm) and irregular collagen fibrils coexist with smaller (30-40 nm) fibrils
• homozygotes show a wider range with fibril diameters varying between 40 and 260 nm; in contrast, wild-type mice display profiles ranging between 40 and 180 nm
• STEM data indicate that mutant collagen fibrils are not uniform in diameter but have bulges (abrupt increases in mass per unit length) along their shafts
• also, homozygotes exhibit a significant reduction of proteoglycan granules and filaments around dermal collagen fibrils relative to wild-type
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• mutants show dermal thinning and loose connective tissue in the hypodermal layer of abdominal skin
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loose skin
(
J:39212
)
|
• homozygotes display skin laxity
• the tail skin is completely detached from the underlying soft tissues with a sharp and bloodless line of rupture along the deeper dermis
|
|
• homozygotes are viable, fertile and anatomically normal but have a thin, fragile skin
• simple application of pressure results in a sharp rupture of the back skin in >50% of homozygotes
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• homozygotes exhibit a significant reduction in skin tensile strength relative to wild-type
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cellular
|
• at 4-14 days after UUO, mutant obstructed kidneys display enhanced apoptosis exclusively in tubular epithelial cells
• in contrast, the degree of apoptosis in interstitial cells remains unaffected
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growth/size/body
|
• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
|
|
• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Ehlers-Danlos syndrome | DOID:13359 |
OMIM:PS130000 |
J:39212 | |
