Analysis Tools
respiratory system
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• while increased apoptosis of epithelial cells is rescued, mice exhibit abnormal branching morphogenesis
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Allele Symbol Allele Name Allele ID |
Bmpr1atm2.1Bhr targeted mutation 2.1, Richard R Behringer MGI:2158390 |
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| Summary |
23 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• while increased apoptosis of epithelial cells is rescued, mice exhibit abnormal branching morphogenesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Joint defects in Bmpr1atm2.1Bhr/Bmpr1atm2.2Bhr Tg(Gdf5-cre,-ALPP)1Kng/0 mice
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• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints
• deterioration similar to that in the foot is also seen in the knee
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• at 7 weeks and 9 months, subchondral sclerosis is seen, especially in the epiphysis of the femur
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• many joints, including those in the foot and the knee, showed a decrease in cartilage however cartilage was normal in non-articular regions
• cartilage formation is reduced and cells with a noncartilaginous appearance are seen in the fibrocartilaginous meniscus that sits between the femur and tibia
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• hypertrophy of the synovial membrane is seen in some joints, particulary in the ankle region
• in severely affected joints the synovial membrane grows into the joint space and this is associated with articular cartilage loss
• synovial hypertophy decreases with age
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• at some sites in the ankles the joints appear to be absent and bones that are normally separated are fused
• in all mutants the second distal tarsal was fused to the central tarsal bone
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• E15.5 expression of early joint markers is decreased in the ankle suggesting the fusion of some of the ankle joints is a result of incomplete segmentation
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• at 7 weeks and 9 months, the domed epiphysis of the tibia is flattened and depressed
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• accelerated cartilage maturation is seen
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• the range of motion of the digit joints is reduced
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• the ability to grasp and remain suspended from a slender rod is significantly reduced
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• the ears are shorter and often lay flatter against the head
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• the ears are shorter than normal
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• soft tissue syndactyly is seen involving the first and second digits that is more severe and more frequent in the forefeet compared to the hindfeet (incidence of 91% and 50%, respectively)
• decreased apoptosis is seen at E14.5 between the first and second digits and in the posterior margin of the fifth digit
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• deterioration similar to that in the foot is also seen in the knee
• digit joints are normal at birth but cartilage is lost as the mutants age; however neutrophils are not seen in the joints
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• the ears are shorter and often lay flatter against the head
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• the ears are shorter than normal
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• the ears are shorter and often lay flatter against the head
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• the ears are shorter than normal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| osteoarthritis | DOID:8398 | J:97780 | ||
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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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• mutants succumb to tumors rapidly, dying between P75 and P90
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• tumors arise from the submandibular salivary glands and are classified as salivary gland squamous cell carcinoma
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• rapidly develop aggressive tumors in the salivary glands
• tumors contain transplantable and hyperproliferative tumor propagating cells (CD24+CD29+)
• treatment of cultured CD24+CD29+ tumor cells with the canonical Wnt inhibitor ICG-001 blocks proliferation of these cells
• CD24+CD29+ tumor propagating cells from salivary gland tumors exhibit unrestricted self-renewal in salisphere culture
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• excessive supernumerary hair follicles in the skin
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| salivary gland carcinoma | DOID:0050904 | J:199091 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die between E10.5 and E11.5
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• E10.5 yolk sacs show only the primary vascular plexus of poorly developed vascular channels instead of large vessels with extensive branching and well-developed capillary network
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• fail to develop beyond E11.5 as indicated by the small size and failure to form digits at E12.5
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• 21 of 69 exhibit pale yolk sacs at E10.5 and by E11.5, all mutants have pale yolk sacs
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• exhibit defective vessel development
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• often show abnormal branching in the trunk
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• E10.5 yolk sacs show only the primary vascular plexus of poorly developed vascular channels instead of large vessels with extensive branching and well-developed capillary network
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• exhibit fewer smooth muscle cell numbers around the dorsal aortas and those that are present do not make close contacts with adjacent endothelial cells
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• often show dilated vessels in the brain
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• at E10.5, the atrioventricular canal endocardial cushion is absent, however the development of the outflow tract cushion appears normal
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• cavity between the pericardial sac and the heart is distended
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• all mutants exhibit hemorrhage throughout the trunk region of the embryo at E11.5
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• embryos surviving to E11.5 are morphologically normal at E10.5 but subsequently succumb to death displaying abdominal hemorrhage
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• exhibit fewer smooth muscle cell numbers around the dorsal aortas and those that are present do not make close contacts with adjacent endothelial cells
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| N |
• exhibit normal embryonic and definitive hematopoiesis
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• cavity between the pericardial sac and the heart is distended
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• at E12.5, embryos are totally pale, although some of them still have red fluid within the amnion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• by E11.5 ectopic outgrowths were observed on the ventral surface of the hindlimb bud
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• at E10, hindlimb buds were smaller
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• mutants were recovered at mendelian frequencies at E10.5
• began to be lost by E11.5 and no live mutant were recovered at E14.5
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• abnormalities of outflow tract and right ventricle was evident by E8.5
• at E13.5 severe abnormalities of outflow tract formation with evident of persistent truncus arteriosus and underdeveloped valves
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• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls
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• decreased apoptosis in outflow tract cushions and increased apoptosis atop the ventricular septum
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• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls
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• decreased apoptosis in outflow tract cushions and increased apoptosis atop the ventricular septum
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• by E11.5 ectopic outgrowths were observed on the ventral surface of the hindlimb bud
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• at E10, hindlimb buds were smaller
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• by E13.5 hindlimb formation was severely abnormal
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• proliferation of ventricular myocardium in the free wall and septum was also decreased in mutants relative to controls
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• decreased apoptosis in outflow tract cushions and increased apoptosis atop the ventricular septum
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• proliferation of developing hindlimb buds was severely decreased
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E18.5, the parietal bone of tamoxifen-treated mice is thicker than in wild-type mice
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• bony areas of tamoxifen-treated mice are loose, discontinuous and disorganized compared to in wild-type mice
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• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice
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• in tamoxifen-treated mice
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• at E18.5, tamoxifen-treated mice exhibit a 30% increase in bone volume to total tissue volume in the calvariae and femora compared to wild-type mice
• tamoxifen-treated mice exhibit increased bone mass in femora and calvariae compared to in wild-type mice
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• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice
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• bone mineralization of calvariae from mice treated with tamoxifen is increased and bone continuity is disrupted compared to in wild-type mice
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• as determined by expression of markers, tamoxifen-treated mice exhibit a modest reduction in E16.5 bone formation compared to in wild-type mice
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• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice
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• in tamoxifen-treated mice
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• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice
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• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice
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• in tamoxifen-treated mice
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• tamoxifen-treated mice exhibit reduced osteoclast activity compared to in wild-type mice
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• at E18.5, the parietal bone of tamoxifen-treated mice is thicker than in wild-type mice
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• as determined by marker expression, tamoxifen-treated mice exhibit reduced osteoclastogenesis compared to wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most homozygotes die in utero or at birth
• some survival to 9 days of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in addition to a normal male reproductive tract, XY mice developed uteri and oviducts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit normal sclerotome formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice
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• hyperplasia in tamoxifen-treated mice
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• foveolar hyperplasia in tamoxifen-treated mice
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• in tamoxifen-treated mice
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• acute and chronic in antral polyps of tamoxifen-treated mice
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• antral and pyloric hyperplasia and distended antral-pyloric region in tamoxifen-treated mice
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• hyperplasia in tamoxifen-treated mice
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• hyperplastic in tamoxifen-treated mice
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• acute and chronic in antral polyps of tamoxifen-treated mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• Background Sensitivity: unlike on an ICR mixed background, all mice exhibit normal lung morphology
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: 46% of mice exhibit lung abnormalities between E16.5, and birth unlike when the transgene is carried on a C57BL/6 background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all mice die or are euthanized within 2 days of birth due to severe respiratory distress
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| N |
• despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal
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• at E16.5, the distal regions of all four lobes are abnormal
• lungs are highly abnormal with large, fluid-filled (emphysematous) sacs
• however, lungs are normal at E12.5
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• at E16.5, the number of more distal branches is reduced and branches are smaller than in wild-type mice
• epithelial cells in the periphery of the lung have a more rounded morphology than in wild-type mice
• epithelial cells cultured in a mesenchyme-free system fail to undergo secondary branching, develop fewer or no buds and exhibit a collapsed and folded morphology compared to wild-type cultures
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• fewer than normal as determined by surfactant C expression
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• despite defects in distal portions of the lungs, proximal bronchi and bronchioles appear normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 45% of 3-month old mutants show longer mitral septal leaflets
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• exhibit a premature disappearance of the myocardial layer in the tricuspid mural leaflet (present at E14.5 but absent at E15.5)
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• the posterior annulus fibrosis is displaced downward into the right ventricular cavity in one of six mutants
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• 36% of 3-month old mutants show longer tricuspid mural leaflets than control valves
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• 3-month old mutants show significantly decreased left ventricular (LV) ejection fraction and increased LV-end-systolic dimension and LV-end-diastolic dimension
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• show a 2-fold increase in left atrial pressure consistent with mitral insufficiency
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• isolated Langendorff perfused mutant hearts show a delta wave with abnormal surface ECG
• hearts with abnormal surface ECG show a base-to-apex activation pattern with evidence of a posterior paraseptal bypass tract
• the annulus fibrosus is disrupted resulting in ventricular preexcitation
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• 6 of 33 mutants, aged between 2 and 6 months, show absence of PR interval
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• 3-month old mutants show significantly decreased left ventricular (LV) ejection fraction and increased LV-end-systolic dimension and LV-end-diastolic dimension
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Ebstein anomaly | DOID:14289 |
OMIM:224700 |
J:111392 | |
| Wolff-Parkinson-White syndrome | DOID:384 |
OMIM:194200 |
J:111392 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• occurs at E12.5 likely due to heart defects
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• embryos are smaller than wild-type littermates at prior to lethality
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• embryos are smaller than wild-type littermates at prior to lethality
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• at E10.5 pouch is thin and underdeveloped compared to wild-type littermates
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• at E10.5 pouch is thin and underdeveloped compared to wild-type littermates
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• embryos display heart defects
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Skeletal abnormalities in Bmpr1btm1Kml/Bmpr1btm1Kml, Bmpr1atm2.1Bhr/Bmpr1atm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1atm2.1Bhr/Bmpr1atm2.1Bhr Bmpr1btm1Kml/Bmpr1btm1Kml Tg(Col2a1-cre)1Bhr/? mice
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• rib cage is flattened
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• rib cage is smaller and flattened
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• generalized chondrodysplasia
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• respiratory distress due to smaller and flattened rib cage
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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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• ectopic distal phalanges are sometimes found
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• although reduced digits is typical, polydactyly sometimes occurs
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• polysyndactyly is common
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• if hindlimbs are present then they are highly malformed
• loss of ventral structures of hindlimbs
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• in many but not all animals
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5 the margin of the pigment epithelium is rough and a ventral discontinuity of the pigment is seen
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• beginning at E11.25-E11.50 excess apoptosis is seen throughout the retina
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• around E11.5 a drastic reduction in cell proliferation is seen in the retina
• Atoh7 expression is not initiated at E11.5 suggesting a failure to initiate retinal neurogenesis
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• beginning at E11.25-E11.50 the retinal neuroectoderm is thinner
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• at E12.5 the margin of the pigment epithelium is rough and a ventral discontinuity of the pigment is seen
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• eyes are small at E12.5 and absent at birth
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• beginning at E11.25-E11.50 excess apoptosis is seen throughout the retina
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• many dorsal retinal ganglion cell axons form ectopic termination zones
• eye size and retinal layer morphology are normal
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• many dorsal retinal ganglion cell axons form ectopic termination zones
• eye size and retinal layer morphology are normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Skeletal abnormalities in Bmpr1btm1Kml/Bmpr1btm1Kml, Bmpr1atm2.1Bhr/Bmpr1atm2.1Bhr Tg(Col2a1-cre)1Bhr/?, and Bmpr1atm2.1Bhr/Bmpr1atm2.1Bhr Bmpr1btm1Kml/Bmpr1btm1Kml Tg(Col2a1-cre)1Bhr/? mice
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• lethality between E17.5 and birth, due to compression of internal organs and eventual heart failure
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• embryos develop short snouts
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• mutants are reduced in size starting at E13.5
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• notochord at E14.5 is disorganized and is embedded within a layer of dense fibroblasts
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• small radius
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• small ulna
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• vertebral column is completely absent at E14.5
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• chondrocytes undergo random and disorganized hypertrophy at P0
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• no vertebrae form by E13.5
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• cartilage elements exhibit reduced rates of proliferation from E13.5 to E16.5 and increased cell apoptosis
• cartilage elements are severely disorganized and do not produce cartilage specific extracellular matrix
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• chondrocyte differentiation is impaired, with appendicular and nasal cavity condensations remaining in a prechondrocytic state
• although cells in prechondrocytic condensations eventually differentiate, they do not undergo the organized differentiation program found in the growth plate
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• the few cartilage condensations that do form are delayed in the prechondrocytic state and never form an organized growth plate
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• severe generalized chondrodysplasia
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• majority of skeletal elements that form through endochondral ossification are absent and the ones that form are rudimentary and malformed
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• small radius
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• small ulna
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• digits by E14.5 have fully formed pericondria but cells within the cores do not exhibit prechondrocyte characteristics
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• embryos develop short limbs
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• embryos develop short tails
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• embryos develop short snouts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no overt eye abnormalities are seen, the retinal layers and retinotectal projections are normal
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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 04/23/2024 MGI 6.23 |
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