Analysis Tools|
Allele Symbol Allele Name Allele ID |
Bmp4+ wild type MGI:1857488 |
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| Summary |
42 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice have reduced numbers of primordial germ cells
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• mice have reduced numbers of primordial germ cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Anterior eye segment abnormalities in Bmp4tm1Blh/Bmp4+ mice
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• less than half as many heterozygotes are born as expected
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• Background Sensitivity: mutants on a C57BL/6J background exhibit variable anterior and posterior segment abnormalities that are reduced on a mixed C3Hf/HeA and C57BL/LiA background
and are rarely seen in mutants on CAST/Ei, 129S6/SvEvTac, or BALB/cJ background
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• variable anterior segment abnormalities in mutants 3-5 months of age
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• abnormal in most eyes
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• small or absent
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• small or absent
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• displaced Schwalbe's line
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• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
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• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
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• pupils are often eccentrically located
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• iris is generally normal, however in some eyes, the iris is hypoplastic and malformed; occasionally the malformation is extensive involving both iris and ciliary body
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• extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles
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• abnormal iridocorneal attachments (anterior synechiae) of variable extent
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• peripheral cornea is often thinner with neovascularization
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• some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze
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• anterior subcapsular and cortical contaracts occur in most mutants
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• anterior subcapsular and cortical contaracts occur in most mutants
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• frequency increased 3 fold
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• variable posterior eye segment abnormalities
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• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
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• abnormalities of the optic nerve head are frequently observed
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• the optic nerve is sometimes absent
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• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
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• retinal ganglion cell layer on average contains about 50% the normal number of cells
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• photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation
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• about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age
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• dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels
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• abnormal persistence of the anterior hyaloid vessels
• posterior hyaloid vessels persist throughout the 17 month period studied and increase in number and size beyond that normally seen at birth
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• irregular white patches in the vitreous and dense vitreous haze in the majority of eyes
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• frequency increased 3 fold
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• in some eyes, both a- and b-wave amplitude are reduced, due in part to poor pupillary dilation, with preferential loss of b-wave relative to a-wave
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• mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure
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• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction
• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1
• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function
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• 2 of 4 circler and 2 of 4 non-circler heterozygotes show reduced neuronal processes in the organ of Corti
• in contrast, the saccule, utricle and ampullae of heterozygotes show normal numbers of neuronal processes
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• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia
• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle
• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues
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• most circling heterozygotes exhibit elevated ABR thresholds across all test frequencies (7 out of 11 mice at 6 kHz and 12 kHz; 8 out of 11 mice at 24 kHz)
• non-circlers display elevated ABR thresholds similar to those of circlers
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• both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing
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• 4 of 6 circling heterozygotes display a significantly reduced number of stereocilia in their ampullae relative to wild-type; the other two circlers show a patchy decrease in the number of stereocilia
• in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle
• non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues
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• neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number
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• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
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• abnormalities of the optic nerve head are frequently observed
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• the optic nerve is sometimes absent
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• circling heterozygotes display low gain ratios with yaw axis rotation in the vestibulo-collic reflex, indicating poorer head stability relative to wild-type mice; poor response is consistent with horizontal semicircular canal dysfunction
• in the pitch axis, circling heterozygotes display as good or better head stability than wild-type mice, with gain ratios being greater or equal to 1
• in contrast, non-circling heterozygotes have gain ratios of greater or equal to 1 in both the yaw and pitch axes, indicating normal VCR function
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• by 2 weeks of age, 10% of heterozygous pups display circling behavior
• 1 of 2 circlers spent 50% of the time circling in a clockwise direction, 17% in a counterclockwise direction and 33% not circling
• the second circler spent 65% of the time circling in a clockwise direction, 1% in a counterclockwise direction and 34% not circling
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• sometimes cystic
• sometimes with abnormal lobulation
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• sometimes cystic
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• female heterozygotes are poorer breeders relative to wild-type females
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• average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup
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• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
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• single cystic kidney in about 12% of heterozygotes
• multiple cysts involving both tubules and glomeruli
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• marked hydronephrosis in 12% of heterozygotes but ureter is undilated
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• cortex of remaining kidney is atrophic
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• single cystic kidney in about 12% of heterozygotes
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• in about 12% of individuals
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• in about 12% of individuals
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• 12% with unilateral anterior polydactyly involving the right hind limb only
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• in about 12% of individuals
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• in about 12% of individuals
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• sometimes cystic
• sometimes with abnormal lobulation
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• sometimes cystic
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• in about 12% of individuals
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• in about 12% of individuals
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• single cystic kidney in about 12% of heterozygotes
• multiple cysts involving both tubules and glomeruli
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• in about 12% of individuals
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Axenfeld-Rieger syndrome type 3 | DOID:0110122 |
OMIM:602482 |
J:82877 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 82% of mice survive to weaning
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• 50% of mice have small or missing 13th rib
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• 50% of mice have small or missing 13th rib
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• 7 of 10 mice develop cervical and thoracic vertebral fusions
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• 7 of 10 mice develop cervical and thoracic vertebral fusions
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• 7 of 10 mice develop formation of the spinous processes in cervical and thoracic vertebra
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• 8% of mice have polycystic or enlarged kidneys
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• 8% of mice have polycystic or enlarged kidneys
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• 13% of mice have small or missing eyes
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• 13% of mice have small or missing eyes
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• at E15 to E 17.5, 10% of mice exhibit a defect in closure of the membranous portion of the ventricular septum
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• 8% of mice have polycystic or enlarged kidneys
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• 8% of mice have polycystic or enlarged kidneys
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Data Sources
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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IMPC - BCM
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: incidence of eye abnormalities is much lower on the 129S6/SvEvTac background than on a C57BL/6J background, with only 1 of 12 mice showing persistent vitreous vessels and abnormal pupil/iris
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• 1 of 12 mice shows persistent vitreous vessels
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• 1 of 12 mice shows abnormal pupil/iris
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• fewer primordial germ cells due to a reduced founder population rather than impaired expansion
• estimated 55% reduction in PGC founder population of mice on the 129S/SvEv, Black Swiss mixed background
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• fewer primordial germ cells due to a reduced founder population rather than impaired expansion
• estimated 55% reduction in PGC founder population of mice on the 129S/SvEv, Black Swiss mixed background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• Background Sensitivity: mice do not display circling behavior on Black Swiss background but a small percentage do on a C57BL/6 background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: only 1 out of 15 mice on a BALB/cJ background exhibit eye abnormalities (persistent vitreous vessels) compared to multiple and variable eye abnormalities seen on a C57BL/6J background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• Background Sensitivity: on a C3Hf/HeA and C57BL/LiA background, fewer mutants exhibit anterior segment abnormalities, with only half showing defects compared to 2/3 of mutants on a C57BL/6J background
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• diabetic mutants (generated by treatment with streptozotocin, STZ) exhibit decreased body weight compared to untreated controls
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| N |
• mice exhibit normal hearing
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• at E12, mice exhibit small or absent lateral plate epithelium compared with wild-type mice with the central part least affected of all the parts
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• higher in the left ear than the right ear
• Background Sensitivity: 70% of females and 62% of males on a mixed 129S2/SvPas and C57BL/6 background exhibit abnormal semicircular canal compared to only 9% of mice on a mixed 129S2/SvPas, C57BL/6, and CBA background
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• the lateral duct and cartilage lining are absent in some mice
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• partially truncated, constricted, or absent in some mice
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• in 37% of females and 24% of males strongly associated with bilateral defects in the lateral semicircular canal
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• diabetic mutants (generated by treatment with streptozotocin, STZ) have increased blood glucose similar to STZ-treated wild-type mice
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• mice show attenuation of mesangial expansion compare to diabetic (STZ-treated) wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer PGCs due to a reduced founder population rather than impaired expansion
(J:53311)
• estimated 62% reduction in PGC founder population of mice on the C57BL/6, CBA mixed background
(J:53311)
• PGCs were absent in 9% of mutant mice on the C57BL/6, CBA mixed background
(J:53311)
• fewer Dppa3+ primordial germ cells than in wild-type mice
(J:199855)
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• Background Sensitivity: only 9% of mice exhibit abnormal semicircular canal on a mixed 129S2/SvPas, C57BL/6, and CBA background compared to 70% of females and 62% of males on a mixed 129S2/SvPas and C57BL/6 background
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• fewer PGCs due to a reduced founder population rather than impaired expansion
(J:53311)
• estimated 62% reduction in PGC founder population of mice on the C57BL/6, CBA mixed background
(J:53311)
• PGCs were absent in 9% of mutant mice on the C57BL/6, CBA mixed background
(J:53311)
• fewer Dppa3+ primordial germ cells than in wild-type mice
(J:199855)
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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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• fewer mice survive to birth than expected
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduced number of primordial germ cells
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• reduced number of primordial germ cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at birth, 53% have grossly identifiably anomalies in the kidneys and urinary tract of these 47% are on the right side only, 15% are on the left side only and 38% are bilateral
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• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells
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• at E12.5, the number of condensed mesenchyme per kidney is reduced; however, nephron density per se is not noticeably reduced
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• at E16.5, condensed and noninduced mesenchymal cells are reduced in number
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• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls
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• at E14.5, in small kidneys the superficial nephrogenic zone is always thinner with a reduced number of nephrogenic components
(J:61482)
• at E16.5, superficial nephrogenic components are lacking; however, the apoptotic activity in the nephrogenic zone is similar to that of wild-type controls
(J:82895)
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• dilated caliceal space with thinning of the renal parenchyma
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• ureterovesical junction-type hydronephrosis is seen in 32% of mice with gross abnormalities
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• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells
• difference in kidney size is detectable at E14.5
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• 60% of mice with gross anomalies show variably reduced kidney mass with microscopically dysplastic regions
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• 8% of mice with gross anomalies show duplex kidney with bifid ureter
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• at E16.5 and P0, ureters are dilated with abnormal winding and kinking in the middle portions
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• at E13.5, the ureter still drains into the Wolffian duct unlike in wild-type controls
(J:61482)
• at E15.5, smooth muscle development of the ureter is impaired; however, the size of the ureter lumen and morphology of the ureter epithelium remain normal
(J:82895)
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• at E15.5, the % of alpha-SMA-expressing smooth muscle cells against total mesenchymal cells around the epithelium at the most cranial portion of the ureter is significantly lower than that in wild-type controls
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• 8% of mice with gross anomalies show duplex kidney with bifid ureter
• arise from duplex kidney and unite caudally to form a single ureter that drains into the bladder
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• variably dilated
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• in the most severely affected embryos the ureter fails to connect to the bladder, connecting instead to the seminal vesicles or vas deferens
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• accompanies hydronephrosis
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• ectopic ureterovesical (UV) junction
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• at E16.5, ectopia of the ureterovesical orifice is observed, with the orifice located closer to the urethral orifice and the distance between the right and left ureteral orifices reduced
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• at E11.5, the secondary buds are smaller
• at E11.5, both the main trunk and the stems of the first 2 branches of the ureter are significantly shorter
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• at E11.5, 2 of 19 mice had accessory buds forming from the main stem of the ureter
• at E11, the primary bud is positioned opposite the approximately 25th somite where in wild-type controls it is opposite the approximately 26th somite
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• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls
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• at E12.5, the common mesonephric duct is longer compared to wild-type controls
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• at E14.5, a significantly higher number of apoptotic (TUNEL+) cells is detected in the stromal cell population of metanephric mesenchyme, unlike in wild-type controls
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• small kidney with regions devoid of nephrogenic components that are instead filled with cysts and stromal mesenchymal cells
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary system disease | DOID:18 | J:61482 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after 3 weeks at 10% oxygen, medial wall thickness in muscularized arteries increases significantly in wild-type mice but is not observed in mutant arteries
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• after 3 weeks at 10% oxygen (hypoxia) , vascular remodeling results in medial wall thickening of muscularized arteries in wild-type mice but is not observed in mutant arteries
• increase in proportion of peripheral muscularized vessels observed in wild-type after hypoxia is significantly reduced in mutant animals exposed to hypoxic conditions
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• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice
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• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia
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• after 3 weeks of hypoxia, mice show little or no increase in right ventricular systolic pressure (RSVP ) compared to wild-type which display a markedly increased RSVP
• after 5 weeks of hypoxia, mutants show consistent fall in RSVP compared to value at 3 weeks of hypoxia
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• under hypoxic conditions, peripheral microvascular endothelial cells do not secrete BMP4 in contrast to cultured wild-type cells
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• proportion of proliferating vascular smooth muscle cells is decreased in hypoxic mutants compared to hypoxic wild-type mice
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• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia
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• after 3 weeks of hypoxia, mice show significant attenuation of right ventricular hypertrophy compared to wild-type animals; after 5 weeks increase in right ventricle weight is attenuated relative to wild-type but not significantly different from mutants after 3 weeks of hypoxia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• fewer mice survive to birth than expected
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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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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• decreased size
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• decreased size
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• missing pieces
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• missing pieces
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• missing pieces
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants show no defects in limb patterning and skeletogenesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Mice deficient singly or in various combinations of Bmp2, Bmp4 and Bmp7 display limb defects
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• mice have more severe skeletal defects than Bmp2-heterozygous, Bmp4-homozygous mice, including significantly thinner skeletal elements
• animals do not have abnormal digit patterns
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E16.5 and E18.5, 50% of mice exhibit abnormal lungs with large sacs
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• at E16.5, cell proliferation lung epithelium and mesenchyme is decreased 50% compared to in wild-type mice while apoptosis is increased compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hindlimb fusion
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• hindlimb fusion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
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• enlarged following doxycycline treatment at E12.5
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• reduced or absent following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
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• reduced following doxycycline treatment at E13.5
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• following doxycycline treatment at E12.5, E11.5 or at E10.5
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• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
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• following doxycycline treatment at E10.5
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• following doxycycline treatment at E12.5 in some mice
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• following doxycycline treatment at E10.5, E12.5, or E13.5
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• shortened face following doxycycline treatment at E10.5
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• following doxycycline treatment at E12.5
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• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
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• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
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• following doxycycline treatment at E10.5 the orientation of the eyes is more anterior
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• following doxycycline treatment at E12.5 in some mice
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• following doxycycline treatment at E10.5, E12.5, or E13.5
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• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
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• following doxycycline treatment at E12.5
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• following doxycycline treatment at E10.5 a strong reduction in rostral bony elements is seen and multiple translucent areas are seen in the skull bones
• later treatment with doxycycline has less dramatic effects on bone morphology
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• enlarged following doxycycline treatment at E12.5
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• reduced or absent following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
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• reduced following doxycycline treatment at E13.5
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• following doxycycline treatment at E12.5, E11.5 or at E10.5
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• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
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• following doxycycline treatment at E10.5
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• following doxycycline treatment at E12.5 in some mice
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• following doxycycline treatment at E10.5, E12.5, or E13.5
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• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
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• reduced or absent following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• following doxycycline treatment at E12.5
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• doxycycline treatment at E11.5 or E10.5 results in a shorter mandible with a more pointed appearance
• doxycycline treatment at E13.5 results in a mandible with a more pointed appearance
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• reduced following doxycycline treatment at E13.5
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• following doxycycline treatment at E12.5, E11.5 or at E10.5
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• doxycycline treatment at E10.5 results in a shorter maxilla with a more pointed appearance
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• following doxycycline treatment at E10.5
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• following doxycycline treatment at E12.5 in some mice
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• following doxycycline treatment at E10.5, E12.5, or E13.5
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• shortened face following doxycycline treatment at E10.5
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• following doxycycline treatment at E12.5
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• enlarged nasal cartilages following doxycycline treatment at E12.5 or E10.5
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• following doxycycline treatment at E10.5 the overall shape of the head is more rounded
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• bifurcated 5th digits frequently seen on forelimbs
• ectopic triphalangeal duplications branching from the 5th metatarsal
• 66% show show similar branched bifurcation of the right 5th digit of the hind limb
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• deformed
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• dual ossification centers along the length of the sternum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• severely reduced as in Ctdnep1tm1Ryn homozygotes
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• severely reduced as in Ctdnep1tm1Ryn homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at E14, neural tube is closed, showing partial phenotypic rescue of neural tube defect seen in Nog-null embryos
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• at E17, lumbar vertebrae are more developed than in Nog-null embryos
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• neural arches are present but noticeably dysmorphic
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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 |
| N |
• kidneys develop and function normally unlike in Grem1tm1Azun homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• both the total number of primordial germ cells and YFP positive primordial germ cells are reduced compared to in wild-type mice
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• both the total number of primordial germ cells and YFP positive primordial germ cells are reduced compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all double heterozygotes exhibit ectopic anterior digits only on the hindlimbs
• extra digit extends from a duplicated metatarsal
• extra digits are triphalangeal
• post axial "nubbins" also seen on the forelimbs of 80% of heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• double heterozygotes are viable, fertile and have normal size and weight
• double heterozygotes have normal size and shape of internal organs and of long bones
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• in one case, digit I was partially triplicated, showing both a complete duplication and a biphalangeal extension of the most anterior extra digit I
• in all cases, none of the extra digits show more than two phalanges but always look like digit I
• no webbing is observed in the affected limbs of double heterozygotes
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• duplication of the first digit is found at a much higher frequency (50%) in double heterozygotes compared to single Bmp4tm1Blh heterozygotes (18%) or Bmp7 heterozygotes (0%); the penetrance of this duplication is, however, lower in double heterozygotes than in Bmp7 homozygous null mice (67%)
• both in Bmp7 homozygous null mice and double heterozygotes, polydactyly primarily affects the right hindlimb than the left hind- or forelimb; however, effects are also observed bilaterally
• most double heterozygotes exhibit incomplete duplication, and the extra digit extends from metatarsal I
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• 44% of double heterozygotes display rib cage defects, including multiple misalignment of the rib pairs
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• as a result of asymmetric rib attachment, the sternum has a sinusoidal appearance in severely affected mice
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• 11% of double heterozygotes have an abnormal xiphoid process: both the cartilaginous and ossified part of the xiphoid process are split medially
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• 44% of double heterozygotes display multiple misalignment of the rib pairs
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• 11% of double heterozygotes display fusion of the ribs; this defect always affects two consecutive costal elements and appears to be limited to a single pair of ribs
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• bifurcated 5th digits frequently seen on forelimbs
• ectopic triphalangeal duplications branching from the 5th metatarsal
• 66% show show similar branched bifurcation of the right 5th digit of the hind limb
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• deformed
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• dual ossification centers along the length of the sternum
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe head malformations with 64% penetrance
• phenotype similar in newborns and at E15.5
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• single nostril
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• low "implantation" of external ears
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• low "implantation" of external ears
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• caudal vertebrae shorter than normal and bone is less dense
• 2 centers of ossification in tail vertebrae and asymmetrical growth leads to kinks
• by E15.5, vertebral bodies of tail were narrower and more rectangular, fewer differentiated chondrocytes
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• 80% of homozygotes with multiple kinks
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• single nostril
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• caudal vertebrae shorter than normal and bone is less dense
• 2 centers of ossification in tail vertebrae and asymmetrical growth leads to kinks
• by E15.5, vertebral bodies of tail were narrower and more rectangular, fewer differentiated chondrocytes
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• lens did not develop
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• retina did not develop
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• single cavity, lack of ventricle medial wall (holoprosencephaly)
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• malformed prosencephalon
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• thickened basal diencephalons at the level of the hypothalamus
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• lateral ganglionic eminence is missing
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• single nostril
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• low "implantation" of external ears
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• apoptotic area in the preaxial mesoderm is completely absent at 12.5 days
• post axial apoptotic areas are normal
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• 100% with unilateral anterior polydactyly involving the hind limbs only
• defect extends into the metatarsals
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• yolk sacs are avascular
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• yolk sacs are avascular
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 18% exhibit microphthalmia
|
| N |
• do not exhibit a vertebral phenotype
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• exhibit suppression of vertebral arch development, a more severe defect than seen in single Bmper homozygotes
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• exhibit a reduction in the ossification of vertebral bodies that is more severe than seen in single Bmper homozygotes
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• exhibit a reduction in size of the vertebral body that is more severe than seen in single Bmper homozygotes
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• exhibit an increase in the frequency of microphthalmia with 100% of double mutants showing the phenotype compared to 18% of double heterozygous mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by E15.5
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• of secondary hair follicles at E16.5
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• by E15.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no external craniofacial defects between E13.5 and E16.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• number of primordial germ cells is lower than in wild-type, but similar to numbers seen in Bmpb8 heterozygotes
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• number of primordial germ cells is lower than in wild-type, but similar to numbers seen in Bmpb8 heterozygotes
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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 01/06/2026 MGI 6.24 |
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