Phenotypes associated with this allele

• Allele Symbol: Adamts10^tm1Dgen
• Allele Name: targeted mutation 1, Deltagen
• Allele ID: MGI:6355992
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adamts10^tm1Dgen/Adamts10^tm1Dgen	B6.Cg-Adamts10^tm1Dgen	MGI:6479043
hm2	Adamts10^tm1Dgen/Adamts10^tm1Dgen	involves: C57BL/6	MGI:8322602
cx3	Adamts10^tm1Dgen/Adamts10^tm1Dgen Adamts17^em1Dhch/Adamts17^em1Dhch	involves: C57BL/6	MGI:8266961
cx4	Adamts10^tm1Dgen/Adamts10^+ Adamts17^em1Dhch/Adamts17^+	involves: C57BL/6	MGI:8322610
cx5	Adamts10^tm1Dgen/Adamts10^tm1Dgen Adamts17^em1Dhch/Adamts17^+	involves: C57BL/6	MGI:8322611
cx6	Adamts10^tm1Dgen/Adamts10^+ Adamts17^em1Dhch/Adamts17^em1Dhch	involves: C57BL/6	MGI:8322613

Genotype
MGI:6479043

hm1

• Allelic Composition: Adamts10^tm1Dgen/Adamts10^tm1Dgen
• Genetic Background: B6.Cg-Adamts10^tm1Dgen

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

mortality/aging

decreased survivor rate ( J:275665 )

• following 10 backcrosses onto the C57BL/6J strain, only 15% of homozygotes are obtained from intercrosses of heterozygous mice at P10; however, no neonatal lethality is observed, suggesting partial embryonic lethality (stage not specified)

• Background Sensitivity: on a hybrid 129 x C57BL/6J genetic background, intercrosses of heterozygotes yield homozygotes in normal Mendelian ratios at P10

prenatal lethality, incomplete penetrance ( J:275665 )

growth/size/body

decreased body weight ( J:275665 )

• surviving mice are externally normal but weigh significantly less than wild-type littermates at 3-, 6-, and 8 weeks of age

• however, body weight is normal in both sexes at 1 week of age

integument

increased skin stiffness ( J:275665 )

• surviving mice exhibit stiff skin, as determined by reduced stretchiness when mice are scruffed

vision/eye

abnormal cilary zonule morphology ( J:275665 )

• ocular zonule fibers are thicker, showing consistently stronger oxytalan staining at 8 days, 6 weeks and 6 months of age

• fibrillin-2 immunostaining is increased in the zonule at 8 days, 6 weeks, and 1 year of age, whereas fibrillin-1 staining is reduced in the zonule at 6 weeks but not at 1 year of age

• however, the ocular zonule appears intact and no ectopia lentis is observed, most likely because the mouse zonule contains fibrillin-2 in addition to fibrillin-1

decreased eye anterior chamber depth ( J:275665 )

• however, eyes appear externally normal during the first 2 years of life; slit lamp examination reveals no anomalies in the cornea, iris or lens while H&E staining indicates normal cornea, ciliary body, and retina histology

• OCT indicates a significant reduction in anterior chamber depth at 3- and 6 weeks of age

abnormal vitreous body morphology ( J:275665 )

• eyes show persistent fibrillin-2 staining in the vitreous in the presumed remnants of the hyaloid vessel matrix both at 8 days and at 24 days after birth, but no detectable change in fibrillin-1 staining

• DAPI staining shows no intravitreal nuclei at 24 days of age, indicating persistence of microfibrils rather than persistence of the hyaloid vasculature

• further biochemical analysis identified fibrillin-2 as a novel ADAMTS10 substrate, providing an explanation for the persistence of ocular fibrillin-2 microfibrils

respiratory system

abnormal pulmonary alveolar duct morphology ( J:275665 )

• adult lungs show a distinct but subtle anomaly characterized by increased alveolarization of the alveolar ducts

• however, no significant change in mean linear intercept analysis of lung parenchyma is observed

cellular

abnormal fibroblast physiology ( J:275665 )

• in a collagen gel contraction assay, isolated dermal fibroblasts contract the gel to a greater extent than wild-type cells

limbs/digits/tail

long ulna ( J:275665 )

♂ • males show a significant increase in ulna length relative to wild-type controls

long femur ( J:275665 )

♀ • females show a significant increase in femur length relative to wild-type controls

skeleton

skeleton phenotype ( J:275665 )

N • adult mice exhibit largely normal skeletal morphology and growth in the appendicular skeleton; distal forelimbs and hindlimbs show no brachydactyly

long ulna ( J:275665 )

♂ • males show a significant increase in ulna length relative to wild-type controls

long femur ( J:275665 )

♀ • females show a significant increase in femur length relative to wild-type controls

cardiovascular system

cardiovascular system phenotype ( J:275665 )

N • mice show normal aortic and mitral valves and cardiac function up to 1 year of age, as determined by echocardiography and histology

Genotype
MGI:8322602

hm2

• Allelic Composition: Adamts10^tm1Dgen/Adamts10^tm1Dgen
• Genetic Background: involves: C57BL/6

growth/size/body

decreased body size ( J:373026 )

• at 4 weeks of age, homozygotes are overtly smaller than wild-type controls

skeleton

skeleton phenotype ( J:373026 )

N • at 4 weeks of age, the lengths of the humerus, radius, ulna, fibula, tibia, first metacarpal, and first metatarsal are NOT shorter than in wild-type controls

N • after 21 days in culture in osteogenic medium, isolated primary rib chondrocytes show no significant differences in alizarin red-positive calcium mineral deposition relative to wild-type chondrocytes

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls

limbs/digits/tail

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls

integument

thin hypodermis ( J:373026 )

• hypodermis thickness is significantly less than in wild-type controls

• however, the hypodermis (panniculus carnosus) muscle layer is not significantly altered

thin dermal layer ( J:373026 )

• dermis thickness is significantly less than in wild-type controls

• however, epidermal layer thickness and hair follicle numbers are not significantly altered

thin skin ( J:373026 )

• at 4 weeks of age, overall thickness of dorsal skin is significantly less than in wild-type controls

cellular

abnormal extracellular matrix morphology ( J:373026 )

• isolated primary skin fibroblasts show an intermediate reduction of fibronectin ECM deposition

• although fibronectin is largely organized in an extracellular fibrillar network, fibroblasts show more prevalent intracellular accumulation of fibrillin-1 in areas where the fibronectin network is sparse or absent

Genotype
MGI:8266961

cx3

• Allelic Composition: Adamts10^tm1Dgen/Adamts10^tm1Dgen; Adamts17^em1Dhch/Adamts17^em1Dhch
• Genetic Background: involves: C57BL/6

mortality/aging

decreased survivor rate ( J:373026 )

• double homozygotes exhibit a 50% survival rate at 23 days of age, with less than 20% surviving to 60 days of age

preweaning lethality, incomplete penetrance ( J:373026 )

• double homozygotes obtained from an intercross of double-heterozygous mice are present at significantly lower frequencies at P7-P10 (3.9% versus expected 6.25%)

postnatal lethality, incomplete penetrance ( J:373026 )

• Kaplan-Meier analysis indicates significant postnatal mortality with ~50% survival at 23 days after birth; cause of death is unknown

growth/size/body

decreased body height ( J:373026 )

• at 4 weeks of age, body weight is significantly lower than that in wild-type controls; however, after normalization of body weight to average femur length, this difference becomes nonsignificant, suggesting proportionate short stature

skeleton

increased diameter of humerus ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the humerus is significantly greater than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

increased diameter of femur ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the femur is significantly greater than in wild-type controls

decreased width of hypertrophic chondrocyte zone ( J:373026 )

• at 4 weeks of age, growth plates exhibit a narrower hypertrophic zone than that in wild-type controls

• however, the proliferative zone remains unchanged

disorganized long bone epiphyseal plate ( J:373026 )

• at 4 weeks of age, Massons trichrome indicates an overall disorganization of the growth plates characterized by normal collagen content but increased collagen intensity in the adjacent bone elements

• columnar organization of proliferating chondrocytes appears to be irregular with more spacing between chondrocyte columns

decreased length of long bones ( J:373026 )

• at 4 weeks of age, mice exhibit the shortest forelimb and hindlimb bones relative to wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short humerus ( J:373026 )

• at 4 weeks of age, the length of the humerus is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short fibula ( J:373026 )

• at 4 weeks of age, the length of the fibula is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short metacarpal bones ( J:373026 )

• at 4 weeks of age, the length of the first metacarpal is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short metatarsal bones ( J:373026 )

• at 4 weeks of age, the length of the first metatarsal is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

limbs/digits/tail

increased diameter of humerus ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the humerus is significantly greater than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short humerus ( J:373026 )

• at 4 weeks of age, the length of the humerus is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

increased diameter of femur ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the femur is significantly greater than in wild-type controls

short fibula ( J:373026 )

• at 4 weeks of age, the length of the fibula is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short metacarpal bones ( J:373026 )

• at 4 weeks of age, the length of the first metacarpal is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short metatarsal bones ( J:373026 )

• at 4 weeks of age, the length of the first metatarsal is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

integument

abnormal hypodermis muscle layer morphology ( J:373026 )

• at 4 weeks of age, the panniculus carnosus muscle underlying mouse skin is significantly thinner than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

• of note, the proportion of the panniculus carnosus muscle to the overall skin thickness is increased

thin hypodermis ( J:373026 )

• hypodermis thickness is severely reduced relative to wild-type controls and significantly less than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

• moreover, the proportion of the hypodermis to the overall skin thickness is severely reduced

decreased hair follicle number ( J:373026 )

• at 4 weeks of age, the number of hair follicles is severely reduced relative to wild-type controls and significantly lower than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

thin dermal layer ( J:373026 )

• dermis thickness is severely reduced relative to wild-type controls and significantly less than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

• of note, the proportion of the dermis to the overall skin thickness is increased

thin epidermis ( J:373026 )

• epidermal layer thickness is slightly but significantly less than in wild-type controls and individual Adamts10^tm1Dgen homozygotes but not less than in Adamts17^em1Dhch homozygotes

thin skin ( J:373026 )

• at 4 weeks of age, overall thickness of dorsal skin is severely reduced relative to wild-type controls and significantly less than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

decreased skin tensile strength ( J:373026 )

• at 4 weeks of age, skin is easily detached and ripped during routine handling (e.g. shaving), indicating skin fragility

muscle

abnormal hypodermis muscle layer morphology ( J:373026 )

• at 4 weeks of age, the panniculus carnosus muscle underlying mouse skin is significantly thinner than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

• of note, the proportion of the panniculus carnosus muscle to the overall skin thickness is increased

cellular

abnormal extracellular matrix morphology ( J:373026 )

• isolated primary skin fibroblasts present at reduced cell numbers show severely impaired fibronectin deposition and thus failure to form an organized fibronectin network concomitant with abnormal intracellular accumulation of fibrillin-1

• lack of fibronectin and subsequently fibrillin-1 ECM deposition could be due to lower cell densities, as fibrillin-1 deposition is known to be dependent on cell density

Genotype
MGI:8322610

cx4

• Allelic Composition: Adamts10^tm1Dgen/Adamts10⁺; Adamts17^em1Dhch/Adamts17⁺
• Genetic Background: involves: C57BL/6

skeleton

skeleton phenotype ( J:373026 )

N • at 4 weeks of age, forelimb and hindlimb bones are not significantly shorter than wild-type bones

Genotype
MGI:8322611

cx5

• Allelic Composition: Adamts10^tm1Dgen/Adamts10^tm1Dgen; Adamts17^em1Dhch/Adamts17⁺
• Genetic Background: involves: C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:373026 )

• only 6.7% (versus expected 12.5%) of mice are obtained from an intercross of double-heterozygous mice at P7-P10

growth/size/body

decreased body size ( J:373026 )

• at 4 weeks of age, mice are overtly smaller than wild-type controls, and show a further reduction in body size relative to individual Adamts10^tm1Dgen homozygotes

decreased body height ( J:373026 )

• at 4 weeks of age, body weight is significantly lower than that in wild-type controls; however, after normalization of body weight to average femur length, this difference becomes nonsignificant, suggesting proportionate short stature

skeleton

increased diameter of humerus ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the humerus is significantly greater than in wild-type controls but not greater than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

increased diameter of femur ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the femur is significantly greater than in wild-type controls but not greater than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

decreased length of long bones ( J:373026 )

• at 4 weeks of age, forelimb and hind limb bones exhibit exacerbated shortening except in the first metacarpal and the first metatarsal

short humerus ( J:373026 )

• at 4 weeks of age, the length of the humerus is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short fibula ( J:373026 )

• at 4 weeks of age, the length of the fibula is significantly shorter than in wild-type controls

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

limbs/digits/tail

increased diameter of humerus ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the humerus is significantly greater than in wild-type controls but not greater than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short humerus ( J:373026 )

• at 4 weeks of age, the length of the humerus is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

increased diameter of femur ( J:373026 )

• at 4 weeks of age, the mid-shaft width of the femur is significantly greater than in wild-type controls but not greater than in individual Adamts10^tm1Dgen or Adamts17^em1Dhch homozygotes

short fibula ( J:373026 )

• at 4 weeks of age, the length of the fibula is significantly shorter than in wild-type controls

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls and individual Adamts10^tm1Dgen homozygotes

Genotype
MGI:8322613

cx6

• Allelic Composition: Adamts10^tm1Dgen/Adamts10⁺; Adamts17^em1Dhch/Adamts17^em1Dhch
• Genetic Background: involves: C57BL/6

skeleton

decreased length of long bones ( J:373026 )

• at 4 weeks of age, forelimb and hindlimb bones exhibit significant shortening relative to wild-type bones, except in the humerus, fibula, the first metacarpal, and the first metatarsal

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls

limbs/digits/tail

short radius ( J:373026 )

• at 4 weeks of age, the length of the radius is significantly shorter than in wild-type controls

short ulna ( J:373026 )

• at 4 weeks of age, the length of the ulna is significantly shorter than in wild-type controls

short femur ( J:373026 )

• at 4 weeks of age, the length of the femur is significantly shorter than in wild-type controls

short tibia ( J:373026 )

• at 4 weeks of age, the length of the tibia is significantly shorter than in wild-type controls