Phenotypes Associated with This Genotype

Genotype
MGI:3047839

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

• ♀: 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

• 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

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

corneal 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