Allele Symbol Allele Name Allele ID |
Bmpr2tm1.1Enl targeted mutation 1.1, En Li MGI:3574812 |
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Summary |
9 genotypes
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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 |
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• female pups develop gray hair mosaically, consistent with the mosaic inactivation of the transgene-carrying X chromosome
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• female pups develop gray hair mosaically, consistent with the mosaic inactivation of the transgene-carrying X chromosome
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
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• male pups show a dramatic hypopigmentation of the hair coat
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• gray-haired skin shows normal melanocyte distribution but substantially less melanin in the hair follicles than control skin
• a reduction in melanin is noted in the hair bulb, where melanocytes form a conical cluster
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• a reduction in melanin is noted in the hair shaft
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• male pups develop uniformly gray coats; gray hair develops during the first period of hair production
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• melanocytes of gray-haired skin produce numerous, dakly-pigmented miniaturized melanosomes, indicating impaired melanosome growth with no significant reduction in melanosome number or pigment-making ability
• failure of melanosomes to grow leads to less production/accumulation of melanin per melanosome
• miniaturized melanosomes are still transferred to epithelial cells of the hair shaft but hair shafts receive less pigment in total, resulting in hypopigmentation and gray color
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• male pups show a dramatic hypopigmentation of the hair coat
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• gray-haired skin shows normal melanocyte distribution but substantially less melanin in the hair follicles than control skin
• a reduction in melanin is noted in the hair bulb, where melanocytes form a conical cluster
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• a reduction in melanin is noted in the hair shaft
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• male pups develop uniformly gray coats; gray hair develops during the first period of hair production
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• at P20, awl, auchene, and zigzag hairs are markedly shorter than normal (consistent with premature entry into catagen), while the normally straightest hair types - guard and awl - are curved
• at P20, awl and auchene hairs lack multiple columns of medullary cells and have instead a single column; as such, awl/auchene hairs possess zigzag-like medullas and widths equivalent to normal zigzag fibers, making them markedly thinner than normal awl/auchene hairs
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• at P20, auchene hairs are markedly shorter and thinner than normal
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• at P20, awl hairs are markedly shorter and thinner than normal
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• coats undergo repeated cycles of hair loss and regrowth throughout life
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• mice exhibit cyclic alopecia
• starting at ~P14, mice undergo total, progressive loss of coat hair in a face-to-tail sequence such that mice are completely bald by ~3 weeks of age; shortly after total coat hair loss, a new hair coat forms in full once more, and this coat is quickly lost again after reaching its maximum length
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• hair follicles enter anagen precociously, leading to a greater number of hair cycles
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• adult mice display hair growth and loss simultaneously, resulting in the appearance of stripes of coat hair and bald skin
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• hair shafts fail to develop hair clubs and exhibit ends of variable length that are tapered, thin, and wavy
• comb-collected hair fibers show the same tapered ends as those gathered with a forceps
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• at P20
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• amorphous clumping of the medullary pigment is observed in all hair types
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• at P20
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• failure to develop hair clubs appears to be the primary cause of total hair loss
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• the hair medulla shows structural disorganization and differentiation defects
• at P11, the hair medulla shows many ectopic BrdU-labeled (proliferating) cells which are normally absent from the differentiating hair shaft
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• medullary cells appear disorganized and fail to form well-defined ladders of pigment bands in all hair types; amorphous clumping of medullary pigment is observed
• medullary trichohyalin is greatly reduced, suggesting that medullary cells fail to differentiate properly
• awl and auchene hair follicles fail to produce multiple columns of medullary cells, generating a single column instead; as such, awl/auchene hairs possess zigzag-like medullas
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• following birth, a dense coat is formed but a subset of hair shafts are thinner than those in control mice
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• at P20, zigzag hairs are markedly shorter than normal
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• mice exhibit excessive nail growth after 2 months of age
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• during catagen, mice show an increase in proliferating cells in the permanent" or superficial segment of the ORS that survives catagen
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• mice exhibit a shift in the anagen/catagen transition, leading to the premature end of anagen and early induction of catagen
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• mice exhibit shortened anagens; similar to the first period of hair production, the second period is also shorter, averaging 10.7 days versus 12.4 days in control mice
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• mice exhibit premature yet prolonged catagens
• catagen starts early with narrowing, amelanotic hair bulbs observed as early as P15, a time when controls continue to grow hair
• by P16-17, all hair follicles have entered catagen but progression through this phase of the hair cycle is slow
• however, no differences in apoptosis are observed during catagen
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• coat follicles always exhibit shortened telogens, as new hair is produced soon after the preceding hair fibers are lost
• at P50, the coat follicles have left the second telogen and uniformly re-entered anagen, whereas those of controls mice are still in the second telogen
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• hair follicles are still regressing at P20, as shown by the presence of extended epithelial strands (involuting remnants of the outer root sheath and hair bulb)
• slowly regressing epithelial strands often appear abnormally curled; concomitant with impaired follicular involution, hair shafts disappear from the skin
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• at P18 (during catagen), BrdU-labeled cells are increased in the superficial segments of the hair follicles
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• at the onset of anagen, mice exhibit a thicker epidermis consistent with an increased number of BrdU-labeled cells in the epidermis
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• amorphous clumping of the medullary pigment is observed in all hair types
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice die around the time of birth
• however, no skin a barrier defect is observed
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• mice exhibit defects in hair development and retention; newborn skin fails to generate coat hair fibers or vibrissae
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• coat follicles typically lack hair bulbs
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• newborns show impaired hair follicle morphogenesis
• however, the epidermis is intact
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• coat and vibrissa hair follicles appear to be slowed or arrested in their development
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• vibrissa follicles possess hair bulbs but are short, showing less downgrowth into the dermis, and generally lack terminally differentiating structures (e.g. the inner root sheath and hair shaft) and terminal differentiation markers (e.g. trichohyalin)
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• vibrissa follicles generally lack the hair shaft
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• mice exhibit normal maxillary and mandibular branches of the trigeminal nerve
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• stunted and prematurely branched at E11.5
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mice are healthy, fertile, and overtly normal with no apparent skin defects
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
N |
• surprisingly, mice are healthy and overtly normal with no apparent skin defects
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• at times, hair fibers show clumping and disorganization of pigment in regions of the hair medulla
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• the hair medulla occasionally appears disorganized
• at times, hair fibers show clumping and disorganization of pigment in regions of the hair medulla
• at P11, the hair medulla contains ectopic BrdU-labeled (proliferating) cells which are normally absent from the differentiating hair shaft
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• medullary trichohyalin is clearly reduced, suggesting that medullary cells fail to differentiate properly
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• at times, hair fibers show clumping and disorganization of pigment in regions of the hair medulla
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♀ | phenotype observed in females |
♂ | phenotype observed in males |
N | normal phenotype |
• mutants with pulmonary hypertension exhibit an increased number of alpha-smooth muscle actin-positive (alphaSMA+) distal pulmonary arteries
• mutants with pulmonary hypertension exhibit an increase in medial wall thickness of alphaSMA+ small pulmonary arteries
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• mutants exhibit a thickening of alphaSMA+ cell layers in small arteries of the pulmonary hypertension lungs and some arteries appear occluded, resembling the concentric vascular lesions in human pulmonary arterial hypertension
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• 50% of mutant lungs show focal leukocyte infiltrations surrounding pulmonary vessels that are not seen in controls; infiltration is more frequent in mice with pulmonary hypertension than in mutants with lower right ventricular systolic pressure
• most of the infiltrating cells are CD68+ monocyte/macrophages
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• ratio of right ventricle to left ventricle plus septum is higher in mutants with pulmonary hypertension than in controls, indicating right ventricle hypertrophy
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• mutants exhibit a higher right ventricular systolic pressure than controls
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• some mutants develop pulmonary hypertension (ventricular systolic pressure > 30 mm Hg)
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• smooth muscle cells in distal pulmonary arteries exhibit increased proliferation index
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• ratio of right ventricle to left ventricle plus septum is higher in mutants with pulmonary hypertension than in controls, indicating right ventricle hypertrophy
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• smooth muscle cells in distal pulmonary arteries exhibit increased proliferation index
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• endothelial cells in distal pulmonary arteries exhibit increased proliferation index
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• 53% of pulmonary hypertension lungs exhibit in situ thrombosis, with lumens of some affected vessels partially or completely occluded by fibrin(ogen)+ thrombi
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• ratio of right ventricle to left ventricle plus septum is higher in mutants with pulmonary hypertension than in controls, indicating right ventricle hypertrophy
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• smooth muscle cells in distal pulmonary arteries exhibit increased proliferation index
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• 50% of mutant lungs show focal leukocyte infiltrations surrounding pulmonary vessels that are not seen in controls; infiltration is more frequent in mice with pulmonary hypertension than in mutants with lower right ventricular systolic pressure
• most of the infiltrating cells are CD68+ monocyte/macrophages
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• endothelial cells in distal pulmonary arteries exhibit increased proliferation index
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
primary pulmonary hypertension | DOID:14557 |
OMIM:178600 OMIM:265400 OMIM:615342 OMIM:615343 OMIM:615344 |
J:158116 |
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 12/17/2024 MGI 6.24 |
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