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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Fmodtm1Aol
targeted mutation 1, Ake Oldberg
MGI:2154550
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Fmodtm1Aol/Fmodtm1Aol involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3050204
hm2
Fmodtm1Aol/Fmodtm1Aol involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:3047838
ht3
Fmodtm1Aol/Fmod+ involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3050205
cx4
Bgntm1Mfy/Y
Fmodtm1Aol/Fmodtm1Aol
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:5698146
cx5
Bgntm1Mfy/Bgntm1Mfy
Fmodtm1Aol/Fmodtm1Aol
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:5698147
cx6
Bgntm1Mfy/Y
Fmodtm1Aol/Fmodtm1Aol
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 MGI:3050192
cx7
Fmodtm1Aol/Fmodtm1Aol
Lumtm1Chak/Lum+
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:3050098
cx8
Fmodtm1Aol/Fmodtm1Aol
Lumtm1Chak/Lumtm1Chak
involves: 129S1/Sv * 129X1/SvJ * CD-1 MGI:3047839


Genotype
MGI:3050204
hm1
Allelic
Composition
Fmodtm1Aol/Fmodtm1Aol
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Abnormal tendon collagen fiber bundles in Fmodtm1Aol/Fmod+ and Fmodtm1Aol/Fmodtm1Aol tails

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

muscle
• 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
• 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




Genotype
MGI:3047838
hm2
Allelic
Composition
Fmodtm1Aol/Fmodtm1Aol
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Altered collagen fibril structure in the flexor digotorum longus tendon of Fmodtm1Aol/Fmodtm1Aol and Fmodtm1Aol/Fmodtm1Aol Lumtm1Chak/Lumtm1Chak mice

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

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

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

skeleton
• homozygotes display an increase in age-dependent osteoarthritis relative to wild-type
• 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
• homozygotes show a 25% reduction in tendon stiffness relative to wild-type
• older homozygotes show degenerative alterations of the articular cartilage

vision/eye
• corneas from homozygous mutant mice are not as clear as wild-type mouse corneas
• homozygotes display a significant increase in ocular axial length relative to wild-type
• mutant scleras contain higher numbers of small-diameter collagen fibrils and fibrils of irregular contours relative to wild-type
• 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




Genotype
MGI:3050205
ht3
Allelic
Composition
Fmodtm1Aol/Fmod+
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Abnormal tendon collagen fiber bundles in Fmodtm1Aol/Fmod+ and Fmodtm1Aol/Fmodtm1Aol tails

muscle
• 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
• 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




Genotype
MGI:5698146
cx4
Allelic
Composition
Bgntm1Mfy/Y
Fmodtm1Aol/Fmodtm1Aol
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bgntm1Mfy mutation (2 available); any Bgn mutation (5 available)
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• 2-fold increase in the percentage of apoptotic cells in the mandibular condylar cartilage at 3 months of age
• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

skeleton
• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation
• 2-fold increase in the percentage of apoptotic cells in the mandibular condylar cartilage at 3 months of age
• 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)
• 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
• extensive articular cartilage destruction by 18 months of age resulting in a decrease in cartilage thickness

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

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




Genotype
MGI:5698147
cx5
Allelic
Composition
Bgntm1Mfy/Bgntm1Mfy
Fmodtm1Aol/Fmodtm1Aol
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bgntm1Mfy mutation (2 available); any Bgn mutation (5 available)
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation

craniofacial
• 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
• 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

skeleton
• PCNA staining is stronger in 3 month old temporomandibular joint fibrocartilage, indicating decreased chondrocyte proliferation
• 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
• 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
• extensive articular cartilage destruction by 18 months of age resulting in a decrease in cartilage thickness




Genotype
MGI:3050192
cx6
Allelic
Composition
Bgntm1Mfy/Y
Fmodtm1Aol/Fmodtm1Aol
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bgntm1Mfy mutation (2 available); any Bgn mutation (5 available)
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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
• double mutants are viable, fertile, and grossly normal but smaller than wild-type or either single mutant

immune system
• 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
• 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
• double mutants show an increased number of very small collagen fibrils (<40 nm) in the quadriceps tendon
• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness

skeleton
• 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
• 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
• double mutants show an increased number of very small collagen fibrils (<40 nm) in the quadriceps tendon
• consistent with an excessive number of very small collagen fibrils, tendons from 1-month-old double mutants show reduced stiffness
• at one month, double mutants show decreased joint flexibility
• double mutants exhibit a dramatic ectopic tendon ossification in knees and ankles which is significantly greater and occurs much earlier than in single mutants




Genotype
MGI:3050098
cx7
Allelic
Composition
Fmodtm1Aol/Fmodtm1Aol
Lumtm1Chak/Lum+
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
Lumtm1Chak mutation (1 available); any Lum mutation (11 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle
• 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
• 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




Genotype
MGI:3047839
cx8
Allelic
Composition
Fmodtm1Aol/Fmodtm1Aol
Lumtm1Chak/Lumtm1Chak
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fmodtm1Aol mutation (0 available); any Fmod mutation (3 available)
Lumtm1Chak mutation (1 available); any Lum mutation (11 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Fmodtm1Aol/Fmodtm1Aol Lumtm1Chak/Lumtm1Chak mice display decreased body size, abnormal gait and abnormal limb morphology

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

cardiovascular system
• double homozygotes show increased vasculature of the myocardium
• double homozygotes display myofiber disorganization but no signs of fibrosis
• in double mutant mice, the weight of the whole heart, normalized for body weight, is decreased relative to wild-type
• double homozygotes bruise easily

growth/size/body
• double mutants are viable and fertile but significantly smaller than wild-type
• double homozygotes show a 23% reduction in body weight relative to wild-type

immune system
• double mutants display age-dependent osteoarthritis

limbs/digits/tail
• double homozygotes have bowed legs
• the distal femur shows a hypertrophic response, providing extra trabecular tissue to support the misaligned patella
• 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
• double homozygotes display myofiber disorganization but no signs of fibrosis
• 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
• 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
• double homozygotes display extreme loss of tendon strength

skeleton
• double mutants display age-dependent osteoarthritis
• the distal femur shows a hypertrophic response, providing extra trabecular tissue to support the misaligned patella
• 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
• 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
• 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
• by 5 months, double homozygotes exhibit severe articular cartilage degeneration due to abnormal usage of the joint

vision/eye
• corneas from double homozygotes appear cloudy and slightly granular relative to wild-type
• 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
• at 1-5 months, 80% of double mutant eyes exhibit several areas of retinal detachment with extensive subretinal debris
• 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
• 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
• taken together, double homozygotes show some of the key features of high myopia, including sclera thinning, increased ocular length, and retinal detachment

integument
• double homozygotes exhibit skin laxity and fragility
• 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)
type I Ehlers-Danlos syndrome DOID:14720 OMIM:130000
J:79115





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last database update
03/24/2020
MGI 6.15
The Jackson Laboratory