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Allele Symbol Allele Name Allele ID |
Dcntm1Ioz targeted mutation 1, Renato V Iozzo MGI:2153002 |
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| Summary |
13 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• chronically infected homozygotes lack a protective niche for Borrelia burgdorferi in joints and skin, resulting in similar spirochete burdens in joints, skin, heart and bladder; spirochete burden remains unaffected during early infection
• in infected joints, protection of B. burgdorferi against immune clearance appears to be specific for dbpA-expressing spirochetes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes are resistant to experimental Lyme disease regardless of the inoculation mode (needle inoculation versus tick transmission of spirochetes); similar effects between the infection dose and tissue colonization by Borrelia burgdorferi are observed by either inoculation procedure
• at low infection doses, most mutant tissues have fewer Borrelia-positive blood cultures relative to wild-type; these differences are generally eliminated at high infection doses
• notably, joints from mutant mice have fewer Borrelia-positive cultures and reduced Borrelia numbers regardless of infection dose; also, mutant joints are found to be less arthritic, regardless of the genetic background of mice
• no differences in Borrelia-positive cultures are generally noted in skin biopsies regardless of genotype or infection dose, although homozygotes have fewer Borrelia-positive skin biopsies than wild-type mice when low-dose tick transmission is used
• homozygotes (BALB/c) are at least as susceptible as wild-type mice to S. aureus-induced septic arthritis (unpublished), arguing against an enhanced host defense against bacterial infections
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in average fibril diameter and range of diameters
• larger fibrils often exhibit an irregular cross-sectional profile
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• at 2 months of age
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• in the tail tendon collagen fibrils show a unimodal rather than bimodal frequency distribution resulting from a relative decrease in number of larger fibrils and a relative increase in number of smaller fibrils
• in the tail tendon the fibril size range and average diameter are increased
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• both average collagen fibril diameter and fibril size range are decreased
• collagen fibrils have irregular cross-sectional profiles
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• in the tail tendon collagen fibrils show a unimodal rather than bimodal frequency distribution resulting from a relative decrease in number of larger fibrils and a relative increase in number of smaller fibrils
• in the tail tendon the fibril size range and average diameter are increased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Dcntm1Ioz/Dcntm1Ioz mice display thin and fragile skin
| N |
• homozygotes do not exhibit any obvious behavioral deficits relative to wild-type mice
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• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
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• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
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| N |
• homozygotes do not exhibit any significant differences in the number of red blood cells, hematocrit or hemoglobin relative to wild-type
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| N |
• homozygotes do not exhibit any significant differences in the levels of albumin, globulin, electrolytes, sodium, and chloride or in the hepatic enzymes, ALT and AST relative to wild-type
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| N |
• homozygotes do not exhibit any significant differences in the number of white blood cells relative to wild-type
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• after UUO, obstructed kidneys from mutant mice show early tubular damage and enhanced infiltration of macrophages relative to wild-type
• at day 53, a significant portion of affected tissue is occupied by infiltrating mononuclear cells, frequently in the form of lymphoid follicles
• in contrast, no differences in the extent of interstitial fibrosis are observed between mutant and wild-type mice
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• in 3-month-old homozygotes, tail tendon collagen fibrils show highly irregular, ragged outlines in cross-section relative to wild-type
• mutant tail tendons exhibit giant fibrils (>660 nm) with multiple lateral fusions; in contrast wild-type tendons have collagen fibrils with an average diameter of ~200 nm
• notably, numerous thin fibrils (40-60 nm) are interspersed with giant fibrils
• abnormal collagen morphology is associated with a decrease in collagen-bound proteoglycans
• although the typical, 67-nm periodicity of type I collagen is preserved, numerous d bands contain no orthogonally arrayed proteoglycan granules
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• at 4-14 days after UUO, mutant obstructed kidneys display enhanced apoptosis exclusively in tubular epithelial cells
• in contrast, the degree of apoptosis in interstitial cells remains unaffected
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• after UUO, obstructed kidneys from mutant mice show early tubular damage and enhanced infiltration of macrophages relative to wild-type
• at day 53, a significant portion of affected tissue is occupied by infiltrating mononuclear cells, frequently in the form of lymphoid follicles
• in contrast, no differences in the extent of interstitial fibrosis are observed between mutant and wild-type mice
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• at 150 days after UUO, pressure-induced injury to wild-type kidneys results in a significant up-regulation of biglycan, decorin, fibrillin-1, and fibrillin-2 expression
• after 150 days, 33% of ligated kidneys from mutant mice exhibit cystic dilatations of Bowman's capsular space and an attenuated upregulation of fibrillin-1; no such changes are observed in ligated kidneys from wild-type mice
• neither cystic dilatations of Bowman's space nor tubular cysts or hemorrhages into the renal pelvis are noted in mutant obstructed kidneys up to 70 days
• in mutants, overexpression of biglycan appears to substitute for decorin with respect to regulation of fibrillin-1 expression
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• at 4-14 days after UUO, mutant obstructed kidneys display a moderate increase in cell proliferation in tubular epithelial cells
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• after unilateral ureteral obstruction (UUO), homozygotes exhibit marked changes in the course and outcome of tubulointerstitial fibrosis of the obstructed kidney relative to wild-type mice; these differences can be explained by specific effects of decorin on apoptosis via p27KIP1 signaling, TGF-beta activity, and collagen turnover
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• prior to unilateral ureteral obstruction (UUO), homozygotes show normal renal morphology and matrix deposition relative to wild-type mice
• after UUO, both wild-type and mutant mice develop hydronephrosis with no major differences in the size of the obstructed and contralateral kidneys up to 35 days
• thereafter, obstructed kidneys from homozygotes become progressively smaller in size and weight
• notably, serum urea and creatinine levels and urinary protein excretion remain unaffected
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• after UUO, end-stage kidneys from mutant mice appear more atrophic than wild-type kidneys as a result of enhanced degradation of type I collagen
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• at day 53 after UUO, tubules with segment-specific differentiation are no longer identifiable in mutant mice (tubular atrophy)
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• at day 7 after UUO, mutant obstructed kidneys display a higher percentage of dilated tubules relative to wild-type obstructed kidneys
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| N |
• radiographically, homozygotes do not exhibit any overt bone defects relative to wild-type mice
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• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
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• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
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• in 3-month-old homozygotes, tail tendon collagen fibrils show highly irregular, ragged outlines in cross-section relative to wild-type
• mutant tail tendons exhibit giant fibrils (>660 nm) with multiple lateral fusions; in contrast wild-type tendons have collagen fibrils with an average diameter of ~200 nm
• notably, numerous thin fibrils (40-60 nm) are interspersed with giant fibrils
• abnormal collagen morphology is associated with a decrease in collagen-bound proteoglycans
• although the typical, 67-nm periodicity of type I collagen is preserved, numerous d bands contain no orthogonally arrayed proteoglycan granules
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| N |
• homozygotes show no significant differences in packing or average size of corneal collagen fibrils relative to wild-type
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• in 3-month-old homozygotes, dermal collagen fibrils are coarser, less orderly packed, and irregular in size and shape relative to wild-type
• in mutant dermis, large (>200 nm) and irregular collagen fibrils coexist with smaller (30-40 nm) fibrils
• homozygotes show a wider range with fibril diameters varying between 40 and 260 nm; in contrast, wild-type mice display profiles ranging between 40 and 180 nm
• STEM data indicate that mutant collagen fibrils are not uniform in diameter but have bulges (abrupt increases in mass per unit length) along their shafts
• also, homozygotes exhibit a significant reduction of proteoglycan granules and filaments around dermal collagen fibrils relative to wild-type
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• mutants show dermal thinning and loose connective tissue in the hypodermal layer of abdominal skin
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• homozygotes display skin laxity
• the tail skin is completely detached from the underlying soft tissues with a sharp and bloodless line of rupture along the deeper dermis
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• homozygotes are viable, fertile and anatomically normal but have a thin, fragile skin
• simple application of pressure results in a sharp rupture of the back skin in >50% of homozygotes
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• homozygotes exhibit a significant reduction in skin tensile strength relative to wild-type
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• at 4-14 days after UUO, mutant obstructed kidneys display enhanced apoptosis exclusively in tubular epithelial cells
• in contrast, the degree of apoptosis in interstitial cells remains unaffected
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• ultrastructurally, the molar periodontal ligament shows abnormal collagen orientation with wide interfibrillar spaces and numerous large-diameter collagen fibers interspersed with very small-diameter collagen fibrils, indicating abnormal lateral fusion of fibrils
• however, homozygotes show normal tooth development and eruption with no signs of periodontal disease
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• in homozygotes, the molar periodontal ligament is hypercellular, showing a ~2-fold increase in the number of fibroblasts relative to wild-type
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Ehlers-Danlos syndrome | DOID:13359 |
OMIM:PS130000 |
J:39212 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• homozygotes do not exhibit any preferential tumor development up to ~2 years of observation
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• ~5% of older homozygotes exhibit salivary gland hyperplasia
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• older homozygotes display a few sporadic cases of gastric mucosa hyperplasia
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• ~5% of older homozygotes exhibit salivary gland hyperplasia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• heterozygotes exhibit a decreased susceptibility to experimental Lyme disease, displaying a reduced arthritis incidence and severity and an intermediate number of Borrelia-positive joints (72%) relative to wild-type (90%) and homozygous mutant mice (47%)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in the risk of preterm birth compared to mice with at least one wild-type allele at either locus
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• rate of progression from plugging to viable pregnancy is reduced
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• at P1
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| female reproductive system disease | DOID:229 | J:180914 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• uniformly atrophic
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• dermal collagen texture is obviously looser, with wide spaces separating collagen bundles
• variability in fibril size is increased compared to either single mutant
• fibril cross-sectional profiles are often ragged or notched
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• tearing of the coat after gentle stretching
• skin ruptures are wider than in Dcntm1Ioz single homozygotes
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• shorter and wider long bones
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• shorter and wider long bones
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• all bone collagen fibrils display a serrated cross-sectional profiles and interfibrillar spaces are wider
• the typical collagenous texture observed in normal bone is replaced with a uniform, glassy appearance of the mineralized matrix in polished and coated samples
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• markedly osteopenic at 2 months of age
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• at 2 months of age
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• at 2 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Ehlers-Danlos syndrome spondylodysplastic type 2 | DOID:0050802 |
OMIM:615349 |
J:91512 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in the risk of preterm birth compared to single homozygous mutants and wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increase in the risk of preterm birth compared to single homozygous mutants and wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• these mutants survive longer than double homozygotes with a 50% mean survival rate of ~6 months, similar to that observed in Trp53tm1Brd mice; surprisingly, no increased incidence of infections is observed
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• similar to double homozygotes, these mutants are predisposed to an accelerated mortality due to increased tumorigenesis, with no differences between male and female occurrence
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• the majority of tumors are high-grade lymphomas arising from the transformation of immature thymocytes
• tumor cells are highly invasive and infiltrate the soft tissues of mediastinum, the salivary glands, the periaortic spaces, the pericardium, and the bronchial wall
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• mutants with thymic lymphomas die of pericardial compression or respiratory distress
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• the majority of tumors are high-grade lymphomas arising from the transformation of immature thymocytes
• tumor cells are highly invasive and infiltrate the soft tissues of mediastinum, the salivary glands, the periaortic spaces, the pericardium, and the bronchial wall
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by ~4 months of age, ~50% of double homozygotes die or need to be sacrificed because of ill health
• by 5 months, ~90% of double homozygotes succumb to tumor growth
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• double homozygotes are predisposed to an accelerated mortality due to increased tumorigenesis, with no differences between male and female occurrence
• double mutants show a significant homogeneity in tumor spectrum and do not exhibit multiple tumors
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• the majority of tumors are high-grade lymphomas arising from the transformation of immature thymocytes
• tumor cells are highly invasive and infiltrate the soft tissues of mediastinum, the salivary glands, the periaortic spaces, the pericardium, and the bronchial wall
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• only one double homozygote developed a high-grade hemangiosarcoma in the submandibular region
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• ~5% of double homozygotes have a significantly enlarged thymus, in the absence of overt tumors
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• ~5% of double homozygotes display no overt neoplasms but show thymic hyperplasia with foci of atypical lymphocytes infiltrating the mediastinal soft tissues and signs of early-invading malignant lymphomas
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• double homozygotes with thymic lymphomas die of pericardial compression or respiratory distress
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• ~5% of double homozygotes have a significantly enlarged thymus, in the absence of overt tumors
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• ~5% of double homozygotes display no overt neoplasms but show thymic hyperplasia with foci of atypical lymphocytes infiltrating the mediastinal soft tissues and signs of early-invading malignant lymphomas
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• ~5% of double homozygotes have a significantly enlarged thymus, in the absence of overt tumors
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• ~5% of double homozygotes display no overt neoplasms but show thymic hyperplasia with foci of atypical lymphocytes infiltrating the mediastinal soft tissues and signs of early-invading malignant lymphomas
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• the majority of tumors are high-grade lymphomas arising from the transformation of immature thymocytes
• tumor cells are highly invasive and infiltrate the soft tissues of mediastinum, the salivary glands, the periaortic spaces, the pericardium, and the bronchial wall
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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 04/30/2024 MGI 6.23 |
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