Phenotypes associated with this allele

• Allele Symbol: Adamts2^tm1Prc
• Allele Name: targeted mutation 1, Darwin J Prockop
• Allele ID: MGI:2388161
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adamts2^tm1Prc/Adamts2^tm1Prc	involves: 129	MGI:2450528
hm2	Adamts2^tm1Prc/Adamts2^tm1Prc	involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6693506
cx3	Adamts14^Gt(511E11)Cmhd/Adamts14^Gt(511E11)Cmhd Adamts2^tm1Prc/Adamts2^tm1Prc	involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6693513

Genotype
MGI:2450528

hm1

• Allelic Composition: Adamts2^tm1Prc/Adamts2^tm1Prc
• Genetic Background: involves: 129

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

craniofacial

abnormal molar morphology ( J:107394 )

• molars show a subtle loss of surface contour, however do not exhibit any other abnormalities in the appendicular, axial, or craniofacial skeleton

triangular face ( J:69141 )

• at 2 months of age, mutant facies begin to look more triangular

short snout ( J:69141 )

• apparent 2 months after birth

reproductive system

abnormal spermatogenesis ( J:69141 )

♂

oligozoospermia ( J:69141 )

♂ • few, if any, active sperm are detected in semen

♂ • significant reduction of mature sperm in testicular sections

male infertility ( J:69141 )

♂ • no vaginal plugs or pregnancies are observed following breeding of male homozygotes with fertile wild-type females

respiratory system

emphysema ( J:107394 )

• lungs show distal air space distension at both 2 weeks and 2 months of age, indicating an emphysema-like appearance without inflammation or fibrosis

skeleton

abnormal molar morphology ( J:107394 )

• molars show a subtle loss of surface contour, however do not exhibit any other abnormalities in the appendicular, axial, or craniofacial skeleton

abnormal xiphoid process morphology ( J:69141 )

• at 2 months of age, the xiphoid is significantly concave and mineralized

integument

abnormal hair follicle morphology ( J:69141 )

• at 2 months of age, hair follicles look thinner

abnormal cutaneous collagen fibril morphology ( J:69141 )

• collagen fibrils in skin are abnormally curled and reduced in thickness by ~50% at 2 months of age

• however, no defects in the structure of cartilage or collagen fibrils of cartilage are observed, eventhough a portion of N-propeptides of type II procollagen was not cleaved

thin skin ( J:69141 )

• at 1-2 months of age, mutant skin feels thinner and softer and tears after handling; becomes more severe with age

growth/size/body

abnormal molar morphology ( J:107394 )

• molars show a subtle loss of surface contour, however do not exhibit any other abnormalities in the appendicular, axial, or craniofacial skeleton

triangular face ( J:69141 )

• at 2 months of age, mutant facies begin to look more triangular

short snout ( J:69141 )

• apparent 2 months after birth

cellular

oligozoospermia ( J:69141 )

♂ • few, if any, active sperm are detected in semen

♂ • significant reduction of mature sperm in testicular sections

Genotype
MGI:6693506

hm2

• Allelic Composition: Adamts2^tm1Prc/Adamts2^tm1Prc
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:271185 )

N • at 6 weeks of age, trans-epidermal water loss is normal, suggesting that the epithelial barrier is functional

abnormal homeostasis ( J:271185 )

• 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), indicating residual amino-procollagen peptidase activity

• in tendon, alpha chains represent ~75% of total type I collagen content

• in cornea, alpha chains represent ~60% of total type I collagen content

• in bone, only fully processed alpha 1 and alpha 2 chains are identified, indicating normal type I procollagen processing

integument

integument phenotype ( J:271185 )

N • at 6 weeks of age, trans-epidermal water loss is normal, suggesting that the epithelial barrier is functional

ruffled hair ( J:271185 )

• at 3 weeks of age, mice are readily identified by a more ruffled fur appearance relative to wild-type controls and single Adamts14^{Gt(511E11)Cmhd} homozygotes

• however, newborn pups are overtly normal

abnormal cutaneous collagen fibril morphology ( J:271185 )

• 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

decreased skin tensile strength ( J:271185 )

• when freshly excised skin strips are clamped into an Instron apparatus and stretched until rupture, tensile strength and % of elongation at rupture are significantly lower than those in wild-type controls

immune system

increased interferon-gamma secretion ( J:271185 )

reproductive system

male infertility ( J:271185 )

skeleton

abnormal tendon collagen fibril morphology ( J:271185 )

• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip

muscle

abnormal tendon collagen fibril morphology ( J:271185 )

• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip

vision/eye

vision/eye phenotype ( J:271185 )

N • despite an increased accumulation of pNalpha1I and pNalpha2I chains in the cornea, collagen fibers exhibit normal ultrastructure and organization

Genotype
MGI:6693513

cx3

• Allelic Composition: Adamts14^{Gt(511E11)Cmhd}/Adamts14^{Gt(511E11)Cmhd}; Adamts2^tm1Prc/Adamts2^tm1Prc
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:271185 )

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

abnormal homeostasis ( J:271185 )

• 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 Adamts2^tm1Prc homozygotes

• in tendon, alpha chains represent ~75% of total type I collagen content, similar to single Adamts2^tm1Prc homozygotes

• in cornea, alpha chains represent ~60% of total type I collagen content, similar to single Adamts2^tm1Prc homozygotes

• in bone, only fully processed alpha 1 and alpha 2 chains are identified indicating normal type I procollagen processing, similar to single Adamts2^tm1Prc homozygotes

integument

integument phenotype ( J:271185 )

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

increased keratinocyte apoptosis ( J:271185 )

• local induction of keratinocyte apoptosis leads to localized disruption of the epidermal barrier and onset of macroscopic epidermal lesions

increased keratinocyte proliferation ( J:271185 )

• proliferative index of the basal keratinocytes is increased only in affected skin regions

dermatitis ( J:271185 )

• double mutant mice develop an intrinsic atopic dermatitis-like syndrome due to immune dysregulation

ruffled hair ( J:271185 )

• at 3 weeks of age, double mutant mice exhibit a ruffled fur appearance, similar to that seen in single Adamts2^tm1Prc homozygotes

abnormal cutaneous collagen fibril morphology ( J:271185 )

• 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 Adamts2^tm1Prc homozygotes

dermal hyperplasia ( J:271185 )

• dermis is hypercellular around the skin lesions

mixed cellular infiltration to dermis ( J:271185 )

• increased dermis cellularity is due to immune cells infiltration and to higher fibroblastic density

thick epidermis ( J:271185 )

• epidermis becomes progressively thickened near lesions; however, epidermis is covered by abundant stratum corneum and contains a well-organized stratum granulosum

spontaneous skin ulceration ( J:271185 )

• 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

decreased skin tensile strength ( J:271185 )

• 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 Adamts2^tm1Prc homozygotes

immune system

cutaneous mastocytosis ( J:271185 )

• a moderately increased number of mastocytes is observed only in affected skin regions

decreased B cell number ( J:271185 )

• 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

increased CD4-positive, alpha-beta T cell number ( J:271185 )

• CD4+ T cell proportion is increased in blood at 10 and 12 weeks of age

decreased CD8-positive, alpha-beta T cell number ( J:271185 )

• CD8+ T cell proportion is decreased in blood at 10 and 12 weeks of age

abnormal T cell activation ( J:271185 )

• CD4+ and CD8+ T cell activation is increased at 8 weeks of age

increased T cell proliferation ( J:271185 )

• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen

increased interferon-gamma secretion ( J:271185 )

increased interleukin-2 secretion ( J:271185 )

dermatitis ( J:271185 )

• double mutant mice develop an intrinsic atopic dermatitis-like syndrome due to immune dysregulation

hematopoietic system

cutaneous mastocytosis ( J:271185 )

• a moderately increased number of mastocytes is observed only in affected skin regions

decreased B cell number ( J:271185 )

• 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

increased CD4-positive, alpha-beta T cell number ( J:271185 )

• CD4+ T cell proportion is increased in blood at 10 and 12 weeks of age

decreased CD8-positive, alpha-beta T cell number ( J:271185 )

• CD8+ T cell proportion is decreased in blood at 10 and 12 weeks of age

abnormal T cell activation ( J:271185 )

• CD4+ and CD8+ T cell activation is increased at 8 weeks of age

increased T cell proliferation ( J:271185 )

• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen

cellular

increased keratinocyte apoptosis ( J:271185 )

• local induction of keratinocyte apoptosis leads to localized disruption of the epidermal barrier and onset of macroscopic epidermal lesions

increased T cell proliferation ( J:271185 )

• mice exhibit a more active and proliferating population of pro-inflammatory CD4+ T lymphocytes in the blood and spleen

increased keratinocyte proliferation ( J:271185 )

• proliferative index of the basal keratinocytes is increased only in affected skin regions

reproductive system

male infertility ( J:271185 )

skeleton

abnormal tendon collagen fibril morphology ( J:271185 )

• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip, similar to those in single Adamts2^tm1Prc homozygotes

muscle

abnormal tendon collagen fibril morphology ( J:271185 )

• some tendon collagen fibrils appear less rounded, esp. fibrils with small diameter or fibril tip, similar to those in single Adamts2^tm1Prc homozygotes

vision/eye

vision/eye phenotype ( J:271185 )

N • despite an increased accumulation of pNalpha1I and pNalpha2I chains in the cornea, collagen fibers exhibit normal ultrastructure and organization