|
Allele Symbol Allele Name Allele ID |
Bmp4tm1Blh targeted mutation 1, Brigid L Hogan MGI:1857137 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
30 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• none survive beyond the egg cylinder stage
|
|
• absence of organized primitive streak
|
|
• hypoplastic extraembryonic mesoderm: small amount can be distinguished
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• none survive beyond the egg cylinder stage
|
|
• absence of organized primitive streak
|
|
• there is a relative paucity of blood islands containing red blood cells in the visceral yolk sac
|
|
• hypoplastic extraembryonic mesoderm: small amount can be distinguished
|
|
• few red blood cells are found in the heart, dorsal aorta, and vessels of an E8.5 embryo
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• a mass of mesodermal cells extending to the apical surface of the ectoderm fills much of the posterior amniotic cavity
|
|
• at the 2 to 8 somite stage, over 75% of embryos show patch or reduced Nodal expression and lack expression in the left lateral plate mesoderm
• in about 65% of embryos at the 3 to 4 somite stage Lefty2 expression is absent from the lateral plate mesoderm
|
|
• an abnormal posterior bulge is present from the headfold to 6 somite stage
|
|
• node is either flat or slightly convex with an irregular periphery in embryos from the headfold to 6 somite stage unlike in controls where it is concave
• one embryo had large endoderm-like cells within the node
|
|
• much of the posterior amniotic cavity is filled up by a mass of mesodermal cells that extends to the apical surface of the ectoderm
|
|
• at the 9 to 10 somite stage in about 50% of embryos the heart tube lies centrally along the midline and shows no signs of looping
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35
(J:51570)
|
|
• failure of lens placode induction
|
|
• at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35
(J:51570)
|
|
• all embryos lacked an allantois
|
|
• no sign of Rathke's pouch formation (either ectodermal thickening or invagination) is noted at E9.5-E9.75
|
|
• no sign of Rathke's pouch formation (either ectodermal thickening or invagination) is noted at E9.5-E9.75
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals die between E7.5 and E10.5; most are arrested at the egg cylinder stage
|
|
• posterior patterning abnormalities
|
|
• embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds
|
|
• visceral yolk sac often have a "blebby" appearance attributable to the paucity of extraembryonic mesoderm and blood islands underlying the endoderm layer
|
|
• paucity of extraembryonic mesoderm underlying the endoderm layer
|
|
• embryos that develop past the egg cylinder stage have a paucity of blood islands
|
|
• absent extraembryonic mesoderm
|
|
• embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• all embryos lacked an allantois
|
|
• absent primordial germ cells
|
|
• absent primordial germ cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos die between E9.5-E11.5
|
|
• are grossly retarded but have undergone turning, have a beating heart and forelimb buds
|
|
• are grossly retarded but have undergone turning, have a beating heart and forelimb buds
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Anterior eye segment abnormalities in Bmp4tm1Blh/Bmp4+ mice
|
• less than half as many heterozygotes are born as expected
|
|
• 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
|
|
• variable anterior segment abnormalities in mutants 3-5 months of age
|
|
• abnormal in most eyes
|
|
• small or absent
|
|
• small or absent
|
|
• displaced Schwalbe's line
|
|
• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
|
|
• hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
|
|
• pupils are often eccentrically located
|
|
• 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
|
|
• extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles
|
|
• abnormal iridocorneal attachments (anterior synechiae) of variable extent
|
|
• peripheral cornea is often thinner with neovascularization
|
|
• some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze
|
|
• anterior subcapsular and cortical contaracts occur in most mutants
|
|
• anterior subcapsular and cortical contaracts occur in most mutants
|
|
• frequency increased 3 fold
|
|
• variable posterior eye segment abnormalities
|
|
• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
|
|
• abnormalities of the optic nerve head are frequently observed
|
|
• the optic nerve is sometimes absent
|
|
• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
|
|
• retinal ganglion cell layer on average contains about 50% the normal number of cells
|
|
• photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation
|
|
• about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age
|
|
• dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels
|
|
• 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
|
|
• irregular white patches in the vitreous and dense vitreous haze in the majority of eyes
|
|
• frequency increased 3 fold
|
|
• 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
|
|
• mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing
|
|
• 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
|
|
• neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number
|
|
• optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
|
|
• abnormalities of the optic nerve head are frequently observed
|
|
• the optic nerve is sometimes absent
|
|
• 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
|
|
• 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
|
 |
• sometimes cystic
• sometimes with abnormal lobulation
|
|
|
• sometimes cystic
|
 |
• female heterozygotes are poorer breeders relative to wild-type females
|
|
• average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup
|
|
• the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
|
|
• single cystic kidney in about 12% of heterozygotes
• multiple cysts involving both tubules and glomeruli
|
|
• marked hydronephrosis in 12% of heterozygotes but ureter is undilated
|
|
• cortex of remaining kidney is atrophic
|
|
• single cystic kidney in about 12% of heterozygotes
|
|
• in about 12% of individuals
|
|
• in about 12% of individuals
|
|
• 12% with unilateral anterior polydactyly involving the right hind limb only
|
|
• in about 12% of individuals
|
|
• in about 12% of individuals
|
|
|
• sometimes cystic
• sometimes with abnormal lobulation
|
|
|
• sometimes cystic
|
|
• in about 12% of individuals
|
|
• single cystic kidney in about 12% of heterozygotes
• multiple cysts involving both tubules and glomeruli
|
|
• in about 12% of individuals
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Axenfeld-Rieger syndrome type 3 | DOID:0110122 |
OMIM:602482 |
J:82877 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• 1 of 12 mice shows persistent vitreous vessels
|
|
• 1 of 12 mice shows abnormal pupil/iris
|
|
• 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
|
|
• 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
|
|
|
| ♀ | 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• diabetic mutants (generated by treatment with streptozotocin, STZ) exhibit decreased body weight compared to untreated controls
|
| N |
• mice exhibit normal hearing
|
|
• 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
|
|
• 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
|
|
• the lateral duct and cartilage lining are absent in some mice
|
|
• partially truncated, constricted, or absent in some mice
|
|
• in 37% of females and 24% of males strongly associated with bilateral defects in the lateral semicircular canal
|
|
• diabetic mutants (generated by treatment with streptozotocin, STZ) have increased blood glucose similar to STZ-treated wild-type mice
|
|
• mice show attenuation of mesangial expansion compare to diabetic (STZ-treated) wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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)
|
|
• 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
|
|
• 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)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• animals at E17.5 have no apparent defects other than eye dysmorphology, but no live births are noted
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• percentage of mice display lateral canal truncation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die between P1 and P7
|
| N |
• no outflow tract abnormalities are seen
|
|
• severe atrial septum primum abnormality resulting in an ostium primum atrial septation defect or partial atrial ventricular canal defect
• however, the atrioventicular and ventricular septa are similar to controls
|
|
• lack normal eyes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cochlear ducts show variability in length
|
|
• less severely affected embryos display truncation of lateral canals
|
|
• not discernible in most severely affected embryos at E13.5
|
|
• not discernible in most severely affected embryos at E13.5
|
|
• malformed in most severely affected embryos at E13.5
|
|
• malformed in most severely affected embryos at E13.5
|
|
• intact endolymphatic duct only is evident in dorsal region of inner ear
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tow thirds of embryos have inner ear defects; more mildly affected embryos show defects in the three ampullae and canals
|
|
• canal defects (in addition to lateral canal truncations) are observed in mildly affected embryos
|
|
• malformed in more severely affected embryos
|
|
• malformed in more severely affected embryos
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no neonates are found
|
|
• at E12.5 about a 20% decrease in proliferation is detected in the atrioventricular cushions but not in other areas of the heart
|
|
• present in 80% of embryos at E15.5 - E16.5
|
|
• single atrioventricular junction with a common valve
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| atrioventricular septal defect | DOID:0050651 |
OMIM:606215 OMIM:614430 OMIM:614474 |
J:86001 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 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
|
|
|
• dual ossification centers along the length of the sternum
|
|
|
• deformed
|
|
|
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severely reduced as in Ctdnep1tm1Ryn homozygotes
|
|
• severely reduced as in Ctdnep1tm1Ryn homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• both the total number of primordial germ cells and YFP positive primordial germ cells are reduced compared to in wild-type mice
|
|
• both the total number of primordial germ cells and YFP positive primordial germ cells are reduced compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
|
| ♀ | 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
|
|
• 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
|
|
• 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
|
|
• 44% of double heterozygotes display rib cage defects, including multiple misalignment of the rib pairs
|
|
• as a result of asymmetric rib attachment, the sternum has a sinusoidal appearance in severely affected mice
|
|
• 11% of double heterozygotes have an abnormal xiphoid process: both the cartilaginous and ossified part of the xiphoid process are split medially
|
|
• 44% of double heterozygotes display multiple misalignment of the rib pairs
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• 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
|
|
|
• dual ossification centers along the length of the sternum
|
|
|
• deformed
|
|
|
|
|
|
| ♀ | 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
|
|
• single nostril
|
|
• low "implantation" of external ears
|
|
• low "implantation" of external ears
|
|
• 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
|
|
• 80% of homozygotes with multiple kinks
|
|
• single nostril
|
|
• 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
|
|
• lens did not develop
|
|
• retina did not develop
|
|
• single cavity, lack of ventricle medial wall (holoprosencephaly)
|
|
• malformed prosencephalon
|
|
• thickened basal diencephalons at the level of the hypothalamus
|
|
• lateral ganglionic eminence is missing
|
|
• single nostril
|
|
• low "implantation" of external ears
|
|
|
| ♀ | 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
|
|
• 100% with unilateral anterior polydactyly involving the hind limbs only
• defect extends into the metatarsals
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• number of primordial germ cells is lower than in wild-type, but similar to numbers seen in Bmpb8 heterozygotes
|
|
• number of primordial germ cells is lower than in wild-type, but similar to numbers seen in Bmpb8 heterozygotes
|
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 04/16/2024 MGI 6.23 |
|
|
|
||
Analysis Tools