All Phenotypes Fmod<tm1Aol> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fmod^tm1Aol/Fmod^tm1Aol	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3050204
hm2	Fmod^tm1Aol/Fmod^tm1Aol	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3047838
ht3	Fmod^tm1Aol/Fmod⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3050205
cx4	Bgn^tm1Mfy/Y Fmod^tm1Aol/Fmod^tm1Aol	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:5698146
cx5	Bgn^tm1Mfy/Bgn^tm1Mfy Fmod^tm1Aol/Fmod^tm1Aol	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:5698147
cx6	Bgn^tm1Mfy/Y Fmod^tm1Aol/Fmod^tm1Aol	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:3050192
cx7	Fmod^tm1Aol/Fmod^tm1Aol Lum^tm1Chak/Lum⁺	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3050098
cx8	Fmod^tm1Aol/Fmod^tm1Aol Lum^tm1Chak/Lum^tm1Chak	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3047839

Allelic Composition	Fmod^tm1Aol/Fmod^tm1Aol
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmod^tm1Aol mutation (1 available); any Fmod mutation (22 available)

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

Abnormal tendon collagen fiber bundles in Fmod^tm1Aol/Fmod⁺ and Fmod^tm1Aol/Fmod^tm1Aol tails

growth/size/body

growth/size/body region phenotype ( J:54069 )

N	• homozygotes are viable, fertile and display no differences in body and organ size or weight relative to wild-type

muscle

abnormal tendon morphology ( J:54069 )

• homozygotes show a significant decrease in endotenon tissue and a 38% reduction in the number of collagen fiber bundles in their tail tendons relative to wild-type

• in transverse sections, mutant bundles appear disorganized with fewer and unevenly distributed cells

• however, longitudinal sections of tail tendons indicate a similar number of cells between wild-type and mutant tendons

• in Achilles tendons, a much larger proportion of mutant collagen fibrils have a thinner diameter, although the range is the same as in wild-type

• at 7- and 20-weeks, homozygotes show a fibril diameter of 128 and 122 nm, respectively (versus 152 and 143 nm, in wild-type); as a result, mutants have ~60% more fibrils than wild-type animals per unit area

skeleton

abnormal tendon morphology ( J:54069 )

• homozygotes show a significant decrease in endotenon tissue and a 38% reduction in the number of collagen fiber bundles in their tail tendons relative to wild-type

• in transverse sections, mutant bundles appear disorganized with fewer and unevenly distributed cells

• however, longitudinal sections of tail tendons indicate a similar number of cells between wild-type and mutant tendons

• in Achilles tendons, a much larger proportion of mutant collagen fibrils have a thinner diameter, although the range is the same as in wild-type

Allelic Composition	Fmod^tm1Aol/Fmod^tm1Aol
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmod^tm1Aol mutation (1 available); any Fmod mutation (22 available)

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

Altered collagen fibril structure in the flexor digotorum longus tendon of Fmod^tm1Aol/Fmod^tm1Aol and Fmod^tm1Aol/Fmod^tm1Aol Lum^tm1Chak/Lum^tm1Chak mice

growth/size/body

growth/size/body region phenotype ( J:79115 )

N	• homozygotes are viable, fertile and display no differences in body size or weight relative to wild-type

immune system

osteoarthritis ( J:79115 )

• homozygotes display an increase in age-dependent osteoarthritis relative to wild-type

muscle

abnormal tendon morphology ( J:65867 )

• at 1-3 months, flexor tendons from homozygotes display collagen fibril irregularities, suggestive of aberrant lateral fusions

• highly irregular profiles include the presence of numerous "cauliflower" collagen fibrils

• at 3 months, mutant tendons show an abnormally large number of immature, small diameter collagen fibrils relative to wild-type

decreased tendon stiffness ( J:79115 )

• homozygotes show a 25% reduction in tendon stiffness relative to wild-type

skeleton

osteoarthritis ( J:79115 )

• homozygotes display an increase in age-dependent osteoarthritis relative to wild-type

abnormal tendon morphology ( J:65867 )

• at 1-3 months, flexor tendons from homozygotes display collagen fibril irregularities, suggestive of aberrant lateral fusions

• highly irregular profiles include the presence of numerous "cauliflower" collagen fibrils

• at 3 months, mutant tendons show an abnormally large number of immature, small diameter collagen fibrils relative to wild-type

decreased tendon stiffness ( J:79115 )

• homozygotes show a 25% reduction in tendon stiffness relative to wild-type

abnormal articular cartilage morphology ( J:79115 )

• older homozygotes show degenerative alterations of the articular cartilage

vision/eye

cornea opacity ( J:83544 )

• corneas from homozygous mutant mice are not as clear as wild-type mouse corneas

abnormal eye size ( J:83544 )

• homozygotes display a significant increase in ocular axial length relative to wild-type

abnormal sclera morphology ( J:83544 )

• mutant scleras contain higher numbers of small-diameter collagen fibrils and fibrils of irregular contours relative to wild-type

sclera thinning ( J:83544 )

• homozygotes show a significant reduction in posterior sclera thickness and a decrease in the number of lamellae

• mutant scleras display lamellar disorganization and occasional fibril-poor areas

Allelic Composition	Fmod^tm1Aol/Fmod⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmod^tm1Aol mutation (1 available); any Fmod mutation (22 available)

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

Abnormal tendon collagen fiber bundles in Fmod^tm1Aol/Fmod⁺ and Fmod^tm1Aol/Fmod^tm1Aol tails

muscle

abnormal tendon morphology ( J:54069 )

• 10-20% of the collagen fiber bundles in heterozygous mutant tendon tail are similar to the abnormal bundles in homozygous null tail tendon

• heterozygotes show a decrease in endotenon tissue and a 15% reduction in the number of collagen fiber bundles in their tail tendons relative to wild-type

• at 7 weeks, collagen fibrils in heterozygous mice have an average diameter and size distribution, which is almost identical to that of wild-type

• surprisingly, at 20 weeks, heterozygous tendons show a broader size distribution and a 10% larger average diameter relative to wild-type

skeleton

abnormal tendon morphology ( J:54069 )

• 10-20% of the collagen fiber bundles in heterozygous mutant tendon tail are similar to the abnormal bundles in homozygous null tail tendon

• heterozygotes show a decrease in endotenon tissue and a 15% reduction in the number of collagen fiber bundles in their tail tendons relative to wild-type

• at 7 weeks, collagen fibrils in heterozygous mice have an average diameter and size distribution, which is almost identical to that of wild-type

• surprisingly, at 20 weeks, heterozygous tendons show a broader size distribution and a 10% larger average diameter relative to wild-type

Allelic Composition	Bgn^tm1Mfy/Y Fmod^tm1Aol/Fmod^tm1Aol
Genetic Background	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bgn^tm1Mfy mutation (2 available); any Bgn mutation (8 available)
Fmod^tm1Aol mutation (1 available); any Fmod mutation (22 available)

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

immune system

accelerated temporomandibular joint osteoarthritis ( J:112779 , J:117908 )

• mice develop first signs of temporomandibular joint osteoarthritis at 6 months of age and show loss of collagen type II expression at its restricted location and expression in the superficial layer of the condylar cartilage (J:112779)

• mice develop accelerated temporomandibular joint osteoarthritis from 6 months of age, showing small vertical clefts in the condylar cartilage and partial disruption of the disk, and loss of regular columnar organization of chondrocytes (J:117908)

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness (J:117908)

cellular

increased apoptosis ( J:112779 )

• 2-fold increase in the percentage of apoptotic cells in the mandibular condylar cartilage at 3 months of age

decreased chondrocyte proliferation ( J:117908 )

• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

skeleton

decreased chondrocyte proliferation ( J:117908 )

• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

abnormal mandible morphology ( J:112779 )

• 2-fold increase in the percentage of apoptotic cells in the mandibular condylar cartilage at 3 months of age

accelerated temporomandibular joint osteoarthritis ( J:112779 , J:117908 )

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness (J:117908)

osteophytes ( J:117908 )

• osteophytes start to form on the mandibular condyle and the glenoid fossa of the temporal bone from 6 months of age and are well developed by 18 months

abnormal articular cartilage morphology ( J:117908 )

• extensive articular cartilage destruction by 18 months of age resulting in a decrease in cartilage thickness

craniofacial

abnormal mandible morphology ( J:112779 )

• 2-fold increase in the percentage of apoptotic cells in the mandibular condylar cartilage at 3 months of age

accelerated temporomandibular joint osteoarthritis ( J:112779 , J:117908 )

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness (J:117908)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoarthritis		DOID:8398		J:112779 , J:117908

Allelic Composition	Bgn^tm1Mfy/Bgn^tm1Mfy Fmod^tm1Aol/Fmod^tm1Aol
Genetic Background	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

Find Mice

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

cellular

decreased chondrocyte proliferation ( J:117908 )

• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

craniofacial

accelerated temporomandibular joint osteoarthritis ( J:117908 )

• from 6 months of age, mice develop accelerated temporomandibular joint osteoarthritis compared to wild-type mice, showing small vertical clefts in the condylar cartilage and partial disruption of the disk, and loss of regular columnar organization of chondrocytes

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness

immune system

accelerated temporomandibular joint osteoarthritis ( J:117908 )

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness

skeleton

decreased chondrocyte proliferation ( J:117908 )

• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

accelerated temporomandibular joint osteoarthritis ( J:117908 )

• by 18 months of age, extensive articular cartilage erosion is seen resulting in a decrease in cartilage thickness

osteophytes ( J:117908 )

• osteophytes start to form on the mandibular condyle and the glenoid fossa of the temporal bone from 6 months of age and are well developed by 18 months

abnormal articular cartilage morphology ( J:117908 )

• extensive articular cartilage destruction by 18 months of age resulting in a decrease in cartilage thickness

Allelic Composition	Bgn^tm1Mfy/Y Fmod^tm1Aol/Fmod^tm1Aol
Genetic Background	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

Find Mice

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

behavior/neurological

abnormal gait ( J:76203 )

• at 3 weeks, double mutants display an abnormal gait characterized by reduced flexibility of knee and ankle joints ("dragging hindlimb"); this phenotype is not observed in either single mutant

• the abnormal gait is transient and occurs on and off on the right or left side; it is not progressive and does not hinder movement in the cages

growth/size/body

decreased body size ( J:76203 )

• double mutants are viable, fertile, and grossly normal but smaller than wild-type or either single mutant

immune system

osteoarthritis ( J:76203 )

• double mutants display a severe premature osteoarthritis and are significantly more affected than wild-type and single mutants at 3 and 9 months

• osteoarthritis starts at 1-2 months and progresses rapidly: there is complete erosion of the articular cartilage in the femur and tibia between 3 and 6 months

• osteoarthritis may be accelerated by moderate levels of forced treadmill running

muscle

abnormal tendon morphology ( J:76203 )

• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness, decreased joint flexibility, and gait impairment

abnormal tendon collagen fibril morphology ( J:76203 )

• double mutants show an increased number of very small collagen fibrils (<40 nm) in the quadriceps tendon

decreased tendon stiffness ( J:76203 )

• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness

skeleton

osteoarthritis ( J:76203 )

• double mutants display a severe premature osteoarthritis and are significantly more affected than wild-type and single mutants at 3 and 9 months

• osteoarthritis starts at 1-2 months and progresses rapidly: there is complete erosion of the articular cartilage in the femur and tibia between 3 and 6 months

• osteoarthritis may be accelerated by moderate levels of forced treadmill running

abnormal tendon morphology ( J:76203 )

• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness, decreased joint flexibility, and gait impairment

abnormal tendon collagen fibril morphology ( J:76203 )

• double mutants show an increased number of very small collagen fibrils (<40 nm) in the quadriceps tendon

decreased tendon stiffness ( J:76203 )

• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness

abnormal joint morphology ( J:76203 )

• at one month, double mutants show decreased joint flexibility

abnormal bone ossification ( J:76203 )

• double mutants exhibit a dramatic ectopic tendon ossification in knees and ankles which is significantly greater and occurs much earlier than in single mutants

Allelic Composition	Fmod^tm1Aol/Fmod^tm1Aol Lum^tm1Chak/Lum⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmod^tm1Aol mutation (1 available); any Fmod mutation (22 available)
Lum^tm1Chak mutation (1 available); any Lum mutation (20 available)

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

muscle

decreased tendon stiffness ( J:83544 )

• compound mutant mice show a 45% reduction in tendon stiffness and a 29% reduction in tensile modulus relative to wild-type

• the severity of stiffness reduction increases with the loss of each functional lumican allele in a lumican dose-dependent fashion

skeleton

decreased tendon stiffness ( J:83544 )

• compound mutant mice show a 45% reduction in tendon stiffness and a 29% reduction in tensile modulus relative to wild-type

• the severity of stiffness reduction increases with the loss of each functional lumican allele in a lumican dose-dependent fashion

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

Fmod^tm1Aol/Fmod^tm1Aol Lum^tm1Chak/Lum^tm1Chak mice display decreased body size, abnormal gait and abnormal limb morphology

behavior/neurological

abnormal gait ( J:79115 )

• double homozygotes exhibit a severe gait impairment and walk on the dorsal part of the foot

cardiovascular system

abnormal blood vessel morphology ( J:79115 )

• double homozygotes show increased vasculature of the myocardium

abnormal myocardial fiber morphology ( J:79115 )

• double homozygotes display myofiber disorganization but no signs of fibrosis

decreased heart weight ( J:79115 )

• in double mutant mice, the weight of the whole heart, normalized for body weight, is decreased relative to wild-type

bruising ( J:79115 )

• double homozygotes bruise easily

growth/size/body

decreased body size ( J:79115 )

• double mutants are viable and fertile but significantly smaller than wild-type

decreased body weight ( J:79115 )

• double homozygotes show a 23% reduction in body weight relative to wild-type

immune system

osteoarthritis ( J:79115 )

• double mutants display age-dependent osteoarthritis

limbs/digits/tail

abnormal limb morphology ( J:79115 )

• double homozygotes have bowed legs

abnormal femur morphology ( J:79115 )

• the distal femur shows a hypertrophic response, providing extra trabecular tissue to support the misaligned patella

abnormal patella morphology ( J:79115 )

• double homozygotes display a 2-fold increase in knee joint deflection, indicating increased joint laxity

• 65% of double homozygotes show a medial misalignment of the patella and a secondary patellar groove

muscle

abnormal myocardial fiber morphology ( J:79115 )

• double homozygotes display myofiber disorganization but no signs of fibrosis

abnormal tendon morphology ( J:79115 )

• at 5 months, tendons from double mutants show abnormal collagen fibrils, many with cauliflower-like contours, indicating abnormal lateral growth

• as in the wild-type, the small diameter fibrils constitute ~25% of the total population in double mutant mice; however, the large diameter population increases to 32% (vs 28% in wild-type), with 7% (vs 5% in wild-type) in the >220-nm range

decreased tendon stiffness ( J:83544 )

• double mutants show a 61% reduction in tendon stiffness and a 49% reduction in tensile modulus relative to wild-type

• the magnitude of reduction in stiffness associated with fibromodulin deficiency depends on the number of functional lumican alleles

muscle weakness ( J:79115 )

• double homozygotes display extreme loss of tendon strength

skeleton

osteoarthritis ( J:79115 )

• double mutants display age-dependent osteoarthritis

abnormal femur morphology ( J:79115 )

• the distal femur shows a hypertrophic response, providing extra trabecular tissue to support the misaligned patella

abnormal patella morphology ( J:79115 )

• double homozygotes display a 2-fold increase in knee joint deflection, indicating increased joint laxity

• 65% of double homozygotes show a medial misalignment of the patella and a secondary patellar groove

abnormal tendon morphology ( J:79115 )

• at 5 months, tendons from double mutants show abnormal collagen fibrils, many with cauliflower-like contours, indicating abnormal lateral growth

decreased tendon stiffness ( J:83544 )

• double mutants show a 61% reduction in tendon stiffness and a 49% reduction in tensile modulus relative to wild-type

• the magnitude of reduction in stiffness associated with fibromodulin deficiency depends on the number of functional lumican alleles

abnormal articular cartilage morphology ( J:79115 )

• by 5 months, double homozygotes exhibit severe articular cartilage degeneration due to abnormal usage of the joint

vision/eye

cornea opacity ( J:83544 )

• corneas from double homozygotes appear cloudy and slightly granular relative to wild-type

abnormal eye size ( J:83544 )

• the double mutant eyes are more elliptical and show a 10% increase in ocular axial length relative to wild-type

• in double homozygotes, the lower the body weight, the greater the ocular axial length

retina detachment ( J:83544 )

• at 1-5 months, 80% of double mutant eyes exhibit several areas of retinal detachment with extensive subretinal debris

abnormal sclera morphology ( J:83544 )

• posterior scleras have a larger fraction of cauliflower-like collagen fibrils, as well as localized areas of small- to very large-diameter fibrils of aberrant contour

sclera thinning ( J:83544 )

• in double homozygotes, the posterior sclera is significantly thinner

• consistent with sclera thinning, the mean number of collagen fibril lamella across the sclera is reduced

• double mutant scleras show significantly higher lamellar disorganization, more fibril-poor areas and abnormal fibril packing relative to wild-type or to either single mutant

high myopia ( J:83544 )

• taken together, double homozygotes show some of the key features of high myopia, including sclera thinning, increased ocular length, and retinal detachment

integument

loose skin ( J:79115 )

• double homozygotes exhibit skin laxity and fragility

decreased skin tensile strength ( J:79115 )

• double homozygotes display a reduction in skin tensile strength relative to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Ehlers-Danlos syndrome classic type 1		DOID:14720	OMIM:130000	J:79115

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