Analysis Tools
mortality/aging
|
• die at 7-8 days of gestation
|
|
Allele Symbol Allele Name Allele ID |
Fbn1Tsk tight skin MGI:1857348 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
16 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die at 7-8 days of gestation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• excessive growth of connective tissue and skeleton
• increase in skeletal size, however body weight is not increased
|
|
• longer skull
|
|
• longer and wider mandible
|
|
• tail and ankle tendons are sgnificantly smaller in size
• in older mice, some tendons show degenerative changes with increased cellularity and decreased amount of collagen
|
|
• in the tail, tendon size reduction is often associated with hyperplasia of the tendon sheath or with accumulation of fluid with the sheath
• ankle tendons show hyperplasia of the tendon sheath as well as hyperplasia of the loose connective tissue between the tendons
|
|
• long bones and girdles are about 5% larger
|
|
• pelvic bone is about 10% larger
|
|
• enlarged in both length and width
|
|
• increase in growth of cartilage
• longer length of the ear cartilage
|
|
• longer length of the fourth tracheal ring
|
|
• costal cartilages are elongated and more bowed than normal
|
|
• enlarged but not as much as the auricles
|
|
• lungs become abnormally distended in enlarged thorax
|
|
• longer length of the fourth tracheal ring
|
|
• tail and ankle tendons are sgnificantly smaller in size
• in older mice, some tendons show degenerative changes with increased cellularity and decreased amount of collagen
|
|
• in the tail, tendon size reduction is often associated with hyperplasia of the tendon sheath or with accumulation of fluid with the sheath
• ankle tendons show hyperplasia of the tendon sheath as well as hyperplasia of the loose connective tissue between the tendons
|
|
• develop a pronounced hump in the shoulder region and hunched posture with age
|
|
• longer skull
|
|
• longer and wider mandible
|
|
• enlarged thorax causing distension of the thoracic viscera
|
|
• hyperplasia of the subcutaneous loose connective tissue
(J:5629)
• in loose connective tissue, exhibit large accumulations of microfibrils in the intercellular space
(J:5629)
• hypodermis is more lamellar
(J:6273)
• fascicles of unusually thin collagen fibrils are found in scattered areas of the hypodermis
(J:6273)
|
|
• hypodermis is substantially thicker
|
|
• dermis fibroblasts often contain greatly distended rough endoplasmic reticulum cisternae
• collagen fibrils within the fascicles of the dermis are less ordered and the fascicles are thinner and more closely packed and appear to bend and twist more along their course
|
|
• fibrous organization of collagen fibrils is not distinctly visible in the hyalinized areas of the superficial dermis
|
|
• reticular dermis of skin is consistently thicker and often more cellular than that of wild-type
|
|
• skin tightness is not seen at birth but develops during the first postnatal week
(J:5629)
• caused by hyperplasia of subcutaneous loose connective tissue
(J:27521)
• skin is firmly bound to subcutaneous and deep muscular tissue
(J:32931)
• skin lacks normal pliability and elasticity
(J:32931)
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Marfan syndrome | DOID:14323 |
OMIM:154700 |
J:21512 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Fbn1Tsk/Fbn1+ skin exhibits abnormal organization and distribution of microfibrillar arrays
|
• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils in the interstitium
(J:6566)
• increased numbers of alveolar macrophages and neutrophils in the interstitium
(J:30961)
|
|
• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils within alveolar air spaces
(J:6566)
• macrophage-neutrophil alveolitis is seen at 3 weeks of age, at a time when emphysematous lesions are not yet present
(J:15018)
• exhibit alveolitis, with increased numbers of alveolar macrophages and neutrophils in the alveolar lumens
(J:30961)
|
|
• enlarged alveolar ducts are first seen at 3 weeks of age
(J:15018)
• dilation of alveolar ducts
(J:30961)
|
|
• exhibit formation of bullae and subpleural cysts and fragmented elastin in alveolar walls
(J:1326)
• enlargement of air spaces with numerous subpleural cysts and scattered bullae
(J:6566)
• at 3 weeks of age, alveoli are flattened but not enlarged, however by 4-6 weeks af age, alveoli are enlarged
(J:15018)
• thinning and destruction of alveolar walls
(J:30961)
• numerous broken alveolar septa and bullous lesions
(J:30961)
• alveoli are irregular in size, with most appearing enlarged
(J:30961)
|
|
• thinning and destruction of alveolar walls
|
|
• develop enlarged alveoli between 4 and 6 weeks of age
(J:15018)
• distension of many alveoli
(J:30961)
• enlarged alveoli are 3 to 4 times larger than normal and show a histologic picture of emphysema
(J:68448)
|
|
• progressive destruction of alveolar septa and increase in collagen deposition in the septa that may result from repair of the lung destruction
|
|
• increase in the number and size of the pores of Kohn
(J:6566)
• alveolar pores in septa are variable in size and increased in number
(J:30961)
|
|
• diffuse thickening of the septa not affected by emphysematous changes, resulting from a progressive increase in collagen
|
|
• emphysematous lesions are seen at 4 weeks of age
(J:15018)
|
|
• dilation of bronchioles
|
|
• increase in total lung capacity
(J:30961)
|
|
• increase in lung compliance
(J:30961)
|
 |
• distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally
|
|
• increase in number and enhanced degree of degranulation of mast cells in the skin
|
|
• develop cell-mediated immunity to elastase-soluble murine lung peptides with age while delayed-type hypersensitivity responses to type I or type IV collagen are not detected
|
|
• develop autoantibodies specific for scleroderma target antigens, with a bias toward the use of VHJ558 genes and JH2 and JK2 segments
(J:14166)
• develop anti-nucleolar antibodies and produce significantly higher titers of autoantibodies specific for scleroderma target antigens (topo I, RNA pol I, and Fc gamma R)
(J:21987)
|
|
• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils in the interstitium
(J:6566)
• increased numbers of alveolar macrophages and neutrophils in the interstitium
(J:30961)
|
|
• presence of focal collections of mononuclear phagocytes, lymphocytes, and neutrophils within alveolar air spaces
(J:6566)
• macrophage-neutrophil alveolitis is seen at 3 weeks of age, at a time when emphysematous lesions are not yet present
(J:15018)
• exhibit alveolitis, with increased numbers of alveolar macrophages and neutrophils in the alveolar lumens
(J:30961)
|
|
|
• distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally
|
|
• increase in number and enhanced degree of degranulation of mast cells in the skin
|
|
• aorta exhibits hyperplasia of loose connective tissue in the adventitia
• collagen fibers in the aorta are increased and microfibrils surrounding elastin in the adventitia of the aorta are not clearly apparent
|
|
• 2.5-fold increase in type VI collagen content in myocardium
(J:17160)
• collagen deposition is increased in the heart
(J:24523)
• type I collagen is increased in the myocardium, perhaps due to reduced activity of negative regulatory sequence
(J:24523)
|
|
• increase in collagen content in the right ventricle at 3 months of age; however, by 16 months of age, collagen content returns to normal levels but there is a shift in collagen type due to an increase in type I collagen, and by 24 months of age, again see an increase in collagen content
|
|
• starts to develop at around 8 months of age
|
|
• thyroid hormone treatment decreases collagen synthesis and stimulates regression of cardiac fibrosis
(J:1562)
• exhibit myocardial fibrosis
(J:24523)
|
|
• 70% increase in collagen content and concentration in the bladder at 5-6 months of age
|
|
• functional bladder capacity appears to be greater
|
| N |
• no aberrant bleeding time after tail vein nick
|
|
|
• distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally
|
|
• increase in width of the subcutaneous fibrous layer with increasing age
|
|
• significantly greater skin biopsy weights, however percent of water-fat is similar to wild-type
• hexosamine, uronic acid, and total glycosaminoglycan content is increased in skin
|
|
• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers and the skin shows abundant irregular and wavy collagen bundles
|
|
• transmission electron microscopy of the upper dermis shows more prominent microfibrillar clusters, which often appear blurred and lacking a discernible striated pattern, but an absence of well-packed elastic fibrils
• although there is a morphologically normal population of skin microfibrils, approximately 45% of the skin microfibril population has abnromal periodic arrays of beads with indistinct filamentous interbeads and extended periodicity of 112 (+/-11) nm relative to 55 (+/-4) nm in normal microfibrils
• the abnormal skin microfibrils have an altered response to calcium chelation by EDTA, with diminished shortening of the periodicity of microfibrils and less prominant appearance of beading compared with control microfibrils, and the large microfibril aggregates fail to dissociate
|
|
• skin is 228 um thick on average instead of the wildtype 132 um
|
|
• develop skin fibrosis which results originally from collagen I and III overexpression and later collagen VI overexpression
(J:26096)
• unlike human scleroderma, fibrosis does not manifest Tgfb1 mRNA in areas of abnormal collagen deposition
(J:26096)
|
|
• cultured skin fibroblasts synthesize almost 5 times more Type I and Type III procollagen mRNA indicating production of excessive amounts of collagen
(J:8140)
• fibroblasts synthesize increased collagen both constitutively and in response to IL4 or TGFB, although IL13 does not increase fibroblast collagen synthesis
(J:68448)
|
|
|
• distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally
|
|
|
• distribution of granulated metrial gland cells, a uterine natural killer-like cell subset, is abnormal during pregnancy, with cells seen in the antimesometral and lateral decidual regions at E8.5 and in regions between implantation sites until E10.5, however their differentiation progresses normally
|
|
• starts to develop at around 8 months of age
|
|
• starts to develop at around 8 months of age
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Marfan syndrome | DOID:14323 |
OMIM:154700 |
J:30961 | |
| pulmonary emphysema | DOID:9675 |
OMIM:130700 |
J:1326 , J:6566 , J:15018 , J:30961 , J:68448 | |
| systemic scleroderma | DOID:418 |
OMIM:181750 |
J:7057 , J:7185 , J:8047 , J:21987 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 3 week old mice fragmentation of elastic lamellae is seen in van-Gieson stained histological sections of the ascending aorta
|
|
• Trichrome-stained sections of adult skin show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer
|
|
• Trichrome-stained sections of adult skin show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 3 week old mice fragmentation of elastic lamellae is seen in van-Gieson stained histological sections of the ascending aorta
|
|
• Trichrome-stained sections of skin of newborn show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer
|
|
• Trichrome-stained sections of skin of newborn show loose connective tissue contains excessive collagen fibers tightly bound to the muscle layer
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• immunohistochemistry of endothelial cells from interscapular skin sections does not show indication of abnormal apoptosis, a symptom found in human scleroderma
|
| N |
• no aberrant bleeding time after tail vein nick
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no Il4 is produced by Th2 cells
|
| N |
• no skin fibrosis develops
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• absence of tight skin heterozygous Tgfb1 null pups from several crosses of heterozygotes is indicative of embryonic loss
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes with normal TGFB1 expression
|
| N |
• unlike tight skin mice, these compound mutants do not develop autoantibodies against the scleroderma antigens topoisomerase I and fibrillin 1
|
|
• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers, the skin is slightly thicker than normal but not as thick as in tight skin mutants with normal TGFB1 expression, and the fat tissue and hair follicles are preserved
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pulmonary emphysema | DOID:9675 |
OMIM:130700 |
J:68448 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes with normal IL4RA expression
|
| N |
• unlike tight skin mice, these compound mutants do not develop autoantibodies against the scleroderma antigens topoisomerase I and fibrillin 1
|
| N |
• the cutaneous hyperplasia found in tight skin heterozygotes is diminished in these compound mutants and the thickness of the skin is normal
|
|
• electron micrographs of skin show a predominance of abnormally small diameter collagen fibers, although there is reduced fibrotic development compared with tight skin mice with wildtype expression of IL4RA
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pulmonary emphysema | DOID:9675 |
OMIM:130700 |
J:68448 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enlarged alveoli and a histologic picture of emphysema are found, similar to that seen in tight skin heterozygotes that are wildtype for Il4ra
|
|
• increased anti-topoisomerase antibodies relative to wildtype, but lower than in tight skin mice wildtype for Il4ra
|
|
• the skin is as thick as tight skin heterozygotes wildtype for Il4ra
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| pulmonary emphysema | DOID:9675 |
OMIM:130700 |
J:68448 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• dermal fibrosis fails to develop
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no skin fibrosis develops
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no Il4 is produced by Th2 cells
|
| N |
• no skin fibrosis develops
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• variable amounts of white-spotting on a slightly diluted coat color
|
|
• variable amounts of white-spotting on a slightly diluted coat color
|
|
• variable amounts of white-spotting on a slightly diluted coat color
|
|
• variable amounts of white-spotting on a slightly diluted coat color
|
|
• progressive development of skin fibrosis similar to that seen in single heterozygous Fbn1 mutant mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• absence of interscapular skin mast cells
|
|
• enlargement of airspaces
|
|
• absence of interscapular skin mast cells
|
|
• white coat and black eyes
|
|
• white coat and black eyes
|
|
• increase in subcutaneous connective tissue, with an accumulation beneath the panniculus carnosus muscle
|
|
• tight skin develops around 7 days of age
|
|
• develop skin fibrosis, indicating that fibrosis is mast cell independent, however the degree of fibrosis development at older ages (5-7 months) is less than in single heterozygous Fbn1 mutant mice, which contain elevated levels of mast cells, indicating that mast cells contribute to fibrosis later in life
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 05/07/2024 MGI 6.23 |
|
|
|
||