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Phenotypes Associated with This Genotype
Genotype
MGI:3047689
Allelic
Composition
Lumtm1Chak/Lumtm1Chak
Genetic
Background
involves: 129S/Sv * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lumtm1Chak mutation (1 available); any Lum mutation (20 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
N
• homozygotes display no major cardiac valvular defects
• homozygotes bruise easily

cellular
• at P10, homozygous mutant mice exhibit increased proliferation and decreased apoptosis of stromal keratocytes during postnatal maturation of the cornea
• in addition, 6-week-old homozygotes show a significant reduction in apoptosis during stromal wound healing
• mutant MEFs display reduced apoptosis relative to wild-type
• in culture, mutant corneal fibroblasts show increased growth relative to wild-type
• mutant mouse embryonic fibroblasts (MEFs) display increased rates of proliferation relative to wild-type

digestive/alimentary system
N
• homozygotes display no major gastrointestinal tract defects

growth/size/body
• homozygotes are viable and fertile; however, ~10-15% of mutant mice are significantly smaller at birth
• homozygotes weigh 70-80% of the body weight of wild-type littermates

muscle
• at P4, mutant tendons show a shift in the relatively homogeneous collagen fibril diameter distributions to larger diameters (72-nm versus 64-nm in wild-type)
• at P10, mutant tendons have relatively equal numbers of fibrils with intermediate diameters (between 65- and 140-nm)
• at 1-3 months, mutant tendons display only slight alterations in collagen fibril diameter relative to wild-type; no differences are detected thereafter

skeleton
• at P4, mutant tendons show a shift in the relatively homogeneous collagen fibril diameter distributions to larger diameters (72-nm versus 64-nm in wild-type)
• at P10, mutant tendons have relatively equal numbers of fibrils with intermediate diameters (between 65- and 140-nm)
• at 1-3 months, mutant tendons display only slight alterations in collagen fibril diameter relative to wild-type; no differences are detected thereafter

vision/eye
• mutant corneas display abnormal arrangement of collagen fibrils and keratinocytes (J:48068)
• TEM revealed that mutant corneal collagen fibrils show a wide range of fiber diameter (i.e. thicker fibrils in addition to fibrils of normal diameter), shape irregularities due to lateral fusions, and increased and non-uniform interfibrillar spacing (J:48068)
• X-ray diffraction patterns from mutant corneas revealed abnormally diffuse interfibrillar reflections (J:70246)
• at 6 months, the average collagen fibril spacing is marginally higher (~7%) in mutant corneas relative to wild-type (J:70246)
• at both 2- and 6-months, X-ray patterns from mutant corneas fail to register any measurable subsidiary X-ray reflection, indicating a broader than normal range of fibril diameters (J:70246)
• beginning at 5 weeks, the mutant stroma appears uniformly hazy and opalescent (J:48068)
• the entire mutant stroma appears bright due to increased backscattered light (J:64730)
• at 4-5 months of age, homozygotes display a 40% reduction in stromal thickness (J:64730)
• at this age, mutant mice also show a 12% reduction in epithelial thickness (J:64730)
• in contrast to wild-type, mutant stroma never increases in thickness from week 1 to 2, remains markedly thinner at 2 weeks, and becomes significantly thinner from week 2 to week 3 after eyelid opening (J:81616)
• the posterior stroma contains numerous large-diameter collagen fibrils, many with irregular contours, indicating abnormal lateral growth
• also, the posterior stroma displays abnormally large fibril aggregates, aberrant fibril packing, and impaired lamellar organization
• notably, the anterior stroma appears relatively unaffected
• homozygotes display normal development of the corneal stroma between E13.5 and E16.5 (J:48068)
• in contrast to wild-type corneal stroma, mutant stroma fails to undergo swelling from P8 to P12 (eyelid opening stage), followed by thinning at P14 (J:81616)
• at 5 to 34 weeks, 44 out of 51 homozygotes show bilateral corneal clouding with a peripheral ring-like clear zone (J:48068)
• corneal opacity is age-dependent: by 8-12 weeks, most homozygotes have cloudy corneas (J:48068)
• also, corneal clouding is progressive: all homozygotes show an increase in opacity over time (J:48068)
• importantly, no mutants exhibit total opacification where iris details are undetectable (J:48068)
• whole eyes from mutant mice exhibit a 25% reduction in total ocular keratan sulfate levels, contributing to reduced corneal transparency (J:64730)
• 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
• in the sclera, the range and distribution of collagen fibril diameter is not severely affected
• on average, homozygotes show a 3-fold increase in backscattering of light, with maximal increase restricted to the posterior stroma (J:64730)
• corneas from wild-type neonates show a rapid loss of light-scattering, decreasing by 50% from P1 to P12 (eyelid opening), concomittant with a 60% decrease in keratocyte density (J:81616)
• in contrast, corneas from mutant neonates show a significant increase in light-scattering at 3 weeks, when stroma thickness is reduced significantly (J:81616)
• in mutant posterior corneas, light-scattering is diffuse as opposed to granular, and remains elevated above wild-type levels, in the absence of significant changes in keratocyte proliferation or differentiation (J:81616)

integument
• homozygotes display a disorganized and loosely arranged dermal connective tissue
• mutant dermal fibroblasts appear disoriented relative to wild-type
• in tail preparations (skin and tendon), dermal regions show increased interfibrillar spacing and a wide range of fiber diameter
• tail skin collagen fibrils are less affected relative to corneal collagen fibrils
• homozygotes exhibit skin laxity and fragility
• homozygotes display an increased incidence of skin lesions
• homozygotes display an 86% 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:48068


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/19/2024
MGI 6.23
The Jackson Laboratory