Strain Name:

B6.129S2-Bmp4tm1Blh/J

Stock Number:

002612

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Availability:

Cryopreserved - Ready for recovery

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
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Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129S2 via D3 ES cell line
GenerationN22p (13-FEB-05)
Generation Definitions
 
Donating Investigator Brigid Hogan,   Duke University Medical Center

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Bmp4tm1Blh targeted mutation mutation die early in embryogenesis. Fifteen to twenty percent of heterozygous mice show developmental defects including polydactyly, craniofacial defects, and cystic kidneys. Heterozygotes have also been reported to show eye abnormalities.

Development
This strain was developed in the laboratory of Dr. Brigid Hogan at Vanderbilt Medical School. The 129S2/SvPas-derived D3 ES cell line was used. The mutation was backcrossed to the C57BL/6 background for 11 generations (N11).

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
Axenfeld-Rieger Syndrome, Type 3; RIEG3 - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Bmp4tm1Blh/Bmp4+

        B6.129S2-Bmp4tm1Blh/J
  • mortality/aging
  • partial perinatal lethality
    • less than half as many heterozygotes are born as expected   (MGI Ref ID J:42445)
  • vision/eye phenotype
  • abnormal eye electrophysiology
    • 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   (MGI Ref ID J:82877)
  • abnormal eye morphology
    • 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   (MGI Ref ID J:82877)
    • abnormal anterior eye segment morphology
      • variable anterior segment abnormalities in mutants 3-5 months of age   (MGI Ref ID J:82877)
      • abnormal cornea morphology
        • extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles   (MGI Ref ID J:82877)
        • anterior iris synechia
          • abnormal iridocorneal attachments (anterior synechiae) of variable extent   (MGI Ref ID J:82877)
        • corneal opacity
          • some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze   (MGI Ref ID J:82877)
        • corneal thinning
          • peripheral cornea is often thinner with neovascularization   (MGI Ref ID J:82877)
      • abnormal iridocorneal angle
        • abnormal in most eyes   (MGI Ref ID J:82877)
        • abnormal canal of Schlemm morphology
          • small or absent   (MGI Ref ID J:82877)
          • absent Schlemm's canal
            • small or absent   (MGI Ref ID J:82877)
        • abnormal line of Schwalbe morphology
          • displaced Schwalbe's line   (MGI Ref ID J:82877)
        • absent trabecular meshwork
          • hypoplastic or absent trabecular meshwork that appears compressed and stalled in development   (MGI Ref ID J:82877)
        • hypoplastic trabecular meshwork
          • hypoplastic or absent trabecular meshwork that appears compressed and stalled in development   (MGI Ref ID J:82877)
      • abnormal placement of pupils
        • pupils are often eccentrically located   (MGI Ref ID J:82877)
      • cataracts   (MGI Ref ID J:82877)
        • anterior cortical cataracts
          • anterior subcapsular and cortical contaracts occur in most mutants   (MGI Ref ID J:82877)
        • anterior subcapsular cataracts
          • anterior subcapsular and cortical contaracts occur in most mutants   (MGI Ref ID J:82877)
      • iris hypoplasia
        • 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   (MGI Ref ID J:82877)
      • irregularly shaped pupil   (MGI Ref ID J:82877)
    • abnormal eye size   (MGI Ref ID J:42445)
      • microphthalmia
        • frequency increased 3 fold   (MGI Ref ID J:42445)
    • abnormal posterior eye segment morphology
      • variable posterior eye segment abnormalities   (MGI Ref ID J:82877)
      • abnormal optic nerve morphology
        • abnormalities of the optic nerve head are frequently observed   (MGI Ref ID J:82877)
        • optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue   (MGI Ref ID J:82877)
        • absent optic nerve
          • the optic nerve is sometimes absent   (MGI Ref ID J:82877)
      • abnormal retina morphology   (MGI Ref ID J:82877)
        • abnormal retinal blood vessel pattern
          • the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type   (MGI Ref ID J:82877)
        • abnormal retinal photoreceptor layer morphology
          • photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation   (MGI Ref ID J:82877)
        • retinal detachment
          • about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age   (MGI Ref ID J:82877)
        • thin retinal ganglion layer
          • retinal ganglion cell layer on average contains about 50% the normal number of cells   (MGI Ref ID J:82877)
        • thin retinal inner nuclear layer   (MGI Ref ID J:82877)
      • abnormal vitreous body morphology
        • dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels   (MGI Ref ID J:82877)
        • opacity of vitreous body
          • irregular white patches in the vitreous and dense vitreous haze in the majority of eyes   (MGI Ref ID J:82877)
        • persistence of hyaloid vascular system
          • abnormal persistence of the anterior hyaloid vessels   (MGI Ref ID J:82877)
          • posterior hyaloid vessels persist throughout the 17 month period studied and increase in number and size beyond that normally seen at birth   (MGI Ref ID J:82877)
    • anophthalmia
      • frequency increased 3 fold   (MGI Ref ID J:42445)
  • ocular hypertension
    • mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure   (MGI Ref ID J:82877)
  • hearing/vestibular/ear phenotype
  • abnormal organ of Corti morphology
    • 2 of 4 circler and 2 of 4 non-circler heterozygotes show reduced neuronal processes in the organ of Corti   (MGI Ref ID J:118380)
    • in contrast, the saccule, utricle and ampullae of heterozygotes show normal numbers of neuronal processes   (MGI Ref ID J:118380)
  • abnormal vestibulocollic reflex
    • 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   (MGI Ref ID J:118380)
    • 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   (MGI Ref ID J:118380)
    • 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   (MGI Ref ID J:118380)
  • decreased brainstem auditory evoked potential
    • 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)   (MGI Ref ID J:118380)
    • non-circlers display elevated ABR thresholds similar to those of circlers   (MGI Ref ID J:118380)
  • decreased vestibular hair cell stereocilia number
    • 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   (MGI Ref ID J:118380)
    • in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle   (MGI Ref ID J:118380)
    • non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues   (MGI Ref ID J:118380)
  • impaired hearing
    • both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing   (MGI Ref ID J:118380)
  • nervous system phenotype
  • abnormal optic nerve morphology
    • abnormalities of the optic nerve head are frequently observed   (MGI Ref ID J:82877)
    • optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue   (MGI Ref ID J:82877)
    • absent optic nerve
      • the optic nerve is sometimes absent   (MGI Ref ID J:82877)
  • abnormal sensory neuron innervation pattern
    • neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number   (MGI Ref ID J:118380)
  • decreased vestibular hair cell stereocilia number
    • 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   (MGI Ref ID J:118380)
    • in contrast, circling heterozygotes show normal stereocilia in the organ of Corti, saccule and utricle   (MGI Ref ID J:118380)
    • non-circling heterozygotes have normal-appearing stereocilia in both auditory and vestibular tissues   (MGI Ref ID J:118380)
  • behavior/neurological phenotype
  • abnormal vestibulocollic reflex
    • 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   (MGI Ref ID J:118380)
    • 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   (MGI Ref ID J:118380)
    • 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   (MGI Ref ID J:118380)
  • circling
    • by 2 weeks of age, 10% of heterozygous pups display circling behavior   (MGI Ref ID J:118380)
    • 1 of 2 circlers spent 50% of the time circling in a clockwise direction, 17% in a counterclockwise direction and 33% not circling   (MGI Ref ID J:118380)
    • the second circler spent 65% of the time circling in a clockwise direction, 1% in a counterclockwise direction and 34% not circling   (MGI Ref ID J:118380)
  • reproductive system phenotype
  • abnormal fertility/fecundity   (MGI Ref ID J:118380)
    • decreased litter size
      • average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup   (MGI Ref ID J:118380)
    • reduced female fertility
      • female heterozygotes are poorer breeders relative to wild-type females   (MGI Ref ID J:118380)
  • abnormal male reproductive system morphology   (MGI Ref ID J:42445)
    • abnormal prostate gland anterior lobe morphology
      • sometimes cystic   (MGI Ref ID J:42445)
      • sometimes with abnormal lobulation   (MGI Ref ID J:42445)
    • abnormal seminiferous tubule morphology
      • sometimes cystic   (MGI Ref ID J:42445)
  • cardiovascular system phenotype
  • abnormal retinal blood vessel pattern
    • the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type   (MGI Ref ID J:82877)
  • renal/urinary system phenotype
  • hydronephrosis
    • marked hydronephrosis in 12% of heterozygotes but ureter is undilated   (MGI Ref ID J:42445)
  • kidney atrophy
    • cortex of remaining kidney is atrophic   (MGI Ref ID J:42445)
  • kidney cysts
    • single cystic kidney in about 12% of heterozygotes   (MGI Ref ID J:42445)
    • multiple cysts involving both tubules and glomeruli   (MGI Ref ID J:42445)
  • single kidney
    • single cystic kidney in about 12% of heterozygotes   (MGI Ref ID J:42445)
  • craniofacial phenotype
  • short frontal bone
    • in about 12% of individuals   (MGI Ref ID J:42445)
  • short nasal bone
    • in about 12% of individuals   (MGI Ref ID J:42445)
  • limbs/digits/tail phenotype
  • polydactyly
    • 12% with unilateral anterior polydactyly involving the right hind limb only   (MGI Ref ID J:42445)
  • skeleton phenotype
  • short frontal bone
    • in about 12% of individuals   (MGI Ref ID J:42445)
  • short nasal bone
    • in about 12% of individuals   (MGI Ref ID J:42445)
  • endocrine/exocrine gland phenotype
  • abnormal prostate gland anterior lobe morphology
    • sometimes cystic   (MGI Ref ID J:42445)
    • sometimes with abnormal lobulation   (MGI Ref ID J:42445)
  • abnormal seminiferous tubule morphology
    • sometimes cystic   (MGI Ref ID J:42445)

Bmp4tm1Blh/Bmp4tm1Blh

        B6.129S2-Bmp4tm1Blh/J
  • mortality/aging
  • complete embryonic lethality before somite formation
    • none survive beyond the egg cylinder stage   (MGI Ref ID J:28717)
  • embryogenesis phenotype
  • abnormal extraembryonic mesoderm development
    • hypoplastic extraembryonic mesoderm: small amount can be distinguished   (MGI Ref ID J:28717)
  • abnormal visceral yolk sac morphology   (MGI Ref ID J:28717)
    • absent visceral yolk sac blood islands
      • there is a relative paucity of blood islands containing red blood cells in the visceral yolk sac   (MGI Ref ID J:28717)
  • failure of primitive streak formation
    • absence of organized primitive streak   (MGI Ref ID J:28717)
  • hematopoietic system phenotype
  • decreased erythrocyte cell number
    • few red blood cells are found in the heart, dorsal aorta, and vessels of an E8.5 embryo   (MGI Ref ID J:28717)

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * C57BL/6 * CBA
  • reproductive system phenotype
  • decreased primordial germ cell number
    • fewer PGCs due to a reduced founder population rather than impaired expansion   (MGI Ref ID J:53311)
    • estimated 62% reduction in PGC founder population of mice on the C57BL/6, CBA mixed background   (MGI Ref ID J:53311)
    • PGCs were absent in 9% of mutant mice on the C57BL/6, CBA mixed background   (MGI Ref ID J:53311)
  • behavior/neurological phenotype
  • circling
    • in 22 of 60 of mice with bilateral lateral semicircular canal defects   (MGI Ref ID J:159227)
  • hearing/vestibular/ear phenotype
  • abnormal lateral semicircular canal morphology
    • 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   (MGI Ref ID J:159227)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * C3Hf/HeA * C57BL/LiA
  • vision/eye phenotype
  • abnormal anterior eye segment morphology
    • 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   (MGI Ref ID J:82877)
    • abnormal iridocorneal angle   (MGI Ref ID J:82877)
    • mydriasis
      • 5 of 13 mutants exhibit enlarged pupils   (MGI Ref ID J:82877)
  • buphthalmos   (MGI Ref ID J:82877)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * CAST/Ei
  • vision/eye phenotype
  • cataracts
    • on a CAST/Ei background, only one of seven mice develops a cataract compared to multiple and variable eye abnormalities in mice on a C57BL/6J background   (MGI Ref ID J:82877)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * 129S6/SvEvTac
  • vision/eye phenotype
  • abnormal eye morphology
    • 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   (MGI Ref ID J:82877)
    • abnormal iris morphology
      • 1 of 12 mice shows persistent vitreous vessels   (MGI Ref ID J:82877)
    • persistence of hyaloid vascular system
      • 1 of 12 mice shows abnormal pupil/iris   (MGI Ref ID J:82877)
  • reproductive system phenotype
  • decreased primordial germ cell number
    • fewer primordial germ cells due to a reduced founder population rather than impaired expansion   (MGI Ref ID J:53311)
    • estimated 55% reduction in PGC founder population of mice on the 129S/SvEv, Black Swiss mixed background   (MGI Ref ID J:53311)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * BALB/cJ
  • vision/eye phenotype
  • persistence of hyaloid vascular system
    • 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   (MGI Ref ID J:82877)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice do not display circling behavior on Black Swiss background but a small percentage do on a C57BL/6 background   (MGI Ref ID J:136636)

Bmp4tm1Blh/Bmp4+

        involves: 129S2/SvPas * C57BL/6
  • growth/size phenotype
  • decreased body weight
    • diabetic mutants (generated by treatment with streptozotocin, STZ) exhibit decreased body weight compared to untreated controls   (MGI Ref ID J:173500)
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype
    • mice exhibit normal hearing   (MGI Ref ID J:159227)
    • abnormal ear development
      • 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   (MGI Ref ID J:159227)
    • abnormal lateral semicircular canal morphology
      • higher in the left ear than the right ear   (MGI Ref ID J:159227)
      • 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   (MGI Ref ID J:159227)
      • absent lateral semicircular canal
        • the lateral duct and cartilage lining are absent in some mice   (MGI Ref ID J:159227)
      • decreased lateral semicircular canal size
        • partially truncated, constricted, or absent in some mice   (MGI Ref ID J:159227)
  • behavior/neurological phenotype
  • circling
    • in 37% of females and 24% of males strongly associated with bilateral defects in the lateral semicircular canal   (MGI Ref ID J:159227)
  • homeostasis/metabolism phenotype
  • increased circulating glucose level
    • diabetic mutants (generated by treatment with streptozotocin, STZ) have increased blood glucose similar to STZ-treated wild-type mice   (MGI Ref ID J:173500)
  • renal/urinary system phenotype
  • abnormal renal glomerulus morphology
    • mice show attenuation of mesangial expansion compare to diabetic (STZ-treated) wild-type   (MGI Ref ID J:173500)

Bmp4tm1Blh/Bmp4tm1Blh

        involves: 129S2/SvPas * Black Swiss
  • mortality/aging
  • complete embryonic lethality during organogenesis
  • growth/size phenotype
  • embryonic growth retardation   (MGI Ref ID J:53311)
    • at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35   (MGI Ref ID J:51570)
  • vision/eye phenotype
  • abnormal lens induction
    • failure of lens placode induction   (MGI Ref ID J:51570)
  • embryogenesis phenotype
  • absent allantois
    • all embryos lacked an allantois   (MGI Ref ID J:53311)
  • embryonic growth retardation   (MGI Ref ID J:53311)
    • at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35   (MGI Ref ID J:51570)
  • reproductive system phenotype
  • absent primordial germ cells   (MGI Ref ID J:53311)
  • endocrine/exocrine gland phenotype
  • abnormal pituitary diverticulum morphology
    • no thickened ectodermal placode precursor ever forms   (MGI Ref ID J:50517)
  • nervous system phenotype
  • abnormal pituitary diverticulum morphology
    • no thickened ectodermal placode precursor ever forms   (MGI Ref ID J:50517)

Bmp4tm1Blh/Bmp4tm1Blh

        involves: 129S2/SvPas * C57BL/6
  • mortality/aging
  • complete embryonic lethality
    • animals die between E7.5 and E10.5; most are arrested at the egg cylinder stage   (MGI Ref ID J:28717)
  • embryogenesis phenotype
  • abnormal extraembryonic mesoderm development
    • absent extraembryonic mesoderm   (MGI Ref ID J:28717)
  • abnormal rostral-caudal axis patterning
    • posterior patterning abnormalities   (MGI Ref ID J:28717)
  • abnormal visceral yolk sac morphology
    • visceral yolk sac often have a "blebby" appearance attributable to the paucity of extraembryonic mesoderm and blood islands underlying the endoderm layer   (MGI Ref ID J:28717)
    • absent visceral yolk sac blood islands
      • embryos that develop past the egg cylinder stage have a paucity of blood islands   (MGI Ref ID J:28717)
  • embryonic growth retardation
    • embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds   (MGI Ref ID J:28717)
  • growth/size phenotype
  • embryonic growth retardation
    • embryos are grossly retarded but have undergone turning, have a beating heart and forelimb buds   (MGI Ref ID J:28717)

Bmp4tm1Blh/Bmp4tm1Blh

        129S2/SvPas-Bmp4tm1Blh
  • mortality/aging
  • complete embryonic lethality before somite formation
    • none survive beyond the egg cylinder stage   (MGI Ref ID J:28717)
  • embryogenesis phenotype
  • abnormal extraembryonic mesoderm development
    • hypoplastic extraembryonic mesoderm: small amount can be distinguished   (MGI Ref ID J:28717)
  • abnormal visceral yolk sac morphology   (MGI Ref ID J:28717)
    • absent visceral yolk sac blood islands   (MGI Ref ID J:28717)
  • failure of primitive streak formation
    • absence of organized primitive streak   (MGI Ref ID J:28717)

Bmp4tm1Blh/Bmp4tm1Blh

        involves: 129S2/SvPas * ICR
  • mortality/aging
  • complete embryonic lethality during organogenesis
    • embryos die between E9.5-E11.5   (MGI Ref ID J:28717)
  • growth/size phenotype
  • embryonic growth retardation
    • are grossly retarded but have undergone turning, have a beating heart and forelimb buds   (MGI Ref ID J:28717)
  • embryogenesis phenotype
  • embryonic growth retardation
    • are grossly retarded but have undergone turning, have a beating heart and forelimb buds   (MGI Ref ID J:28717)

Bmp4tm1Blh/Bmp4tm1Blh

        involves: 129S2/SvPas * C57BL/6 * CBA
  • mortality/aging
  • complete prenatal lethality   (MGI Ref ID J:53311)
  • embryogenesis phenotype
  • absent allantois
    • all embryos lacked an allantois   (MGI Ref ID J:53311)
  • embryonic growth retardation   (MGI Ref ID J:53311)
  • reproductive system phenotype
  • absent primordial germ cells
    • absent primordial germ cells   (MGI Ref ID J:53311)
  • growth/size phenotype
  • embryonic growth retardation   (MGI Ref ID J:53311)

Bmp4tm1Blh/Bmp4tm1Blh

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss
  • embryogenesis phenotype
  • abnormal mesoderm development
    • a mass of mesodermal cells extending to the apical surface of the ectoderm fills much of the posterior amniotic cavity   (MGI Ref ID J:79391)
    • abnormal lateral plate mesoderm morphology
      • 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   (MGI Ref ID J:79391)
      • in about 65% of embryos at the 3 to 4 somite stage Lefty2 expression is absent from the lateral plate mesoderm   (MGI Ref ID J:79391)
  • abnormal primitive streak morphology
    • an abnormal posterior bulge is present from the headfold to 6 somite stage   (MGI Ref ID J:79391)
    • abnormal primitive node morphology
      • 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   (MGI Ref ID J:79391)
      • one embryo had large endoderm-like cells within the node   (MGI Ref ID J:79391)
  • cardiovascular system phenotype
  • abnormal heart looping
    • 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   (MGI Ref ID J:79391)

Bmp4tm1Blh/Bmp4tm4Blh

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL
  • hearing/vestibular/ear phenotype
  • abnormal semicircular canal morphology
    • percentage of mice display lateral canal truncation   (MGI Ref ID J:136636)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Bmp4tm1Blh related

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
Eye Defects
Growth Defects
Internal/Organ Defects
      kidney
Skeletal Defects

Endocrine Deficiency Research
Bone/Bone Marrow Defects
Gonad Defects
Kidney Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Internal/Organ Research
Kidney Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Fertility Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Bmp4tm1Blh
Allele Name targeted mutation 1, Brigid L Hogan
Allele Type Targeted (knock-out)
Common Name(s) Bmp-4tm1blh; Bmp4-; Bmp4delta; Bmp4tm1;
Mutation Made By Brigid Hogan,   Duke University Medical Center
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Bmp4, bone morphogenetic protein 4
Chromosome 14
Gene Common Name(s) BMP2B; BMP2B1; BOMPR4A; Bmp-4; Bmp2b; Bmp2b-1; Bmp2b1; MCOPS6; OFC11; ZYME; bone morphogenetic protein 2b; bone morphogenetic protein 2b 1;
Molecular Note A neomycin selection cassette replaced a genomic fragment containing all of the coding sequence of the gene after the seventh codon of exon 1. An oligonucleotide encoding a stop codon in all three reading frames was also inserted into exon 2. [MGI Ref ID J:28717]

Genotyping

Genotyping Information

Genotyping Protocols

Bmp4tm1Blh, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Winnier G; Blessing M; Labosky PA; Hogan BL. 1995. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9(17):2105-16. [PubMed: 7657163]  [MGI Ref ID J:28717]

Additional References

Dunn NR; Winnier GE; Hargett LK; Schrick JJ; Fogo AB; Hogan BL. 1997. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 188(2):235-47. [PubMed: 9268572]  [MGI Ref ID J:42445]

Paine-Saunders S; Viviano BL; Zupicich J; Skarnes WC; Saunders S. 2000. glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev Biol 225(1):179-87. [PubMed: 10964473]  [MGI Ref ID J:64330]

Bmp4tm1Blh related

Blauwkamp MN; Beyer LA; Kabara L; Takemura K; Buck T; King WM; Dolan DF; Barald KF; Raphael Y; Koenig RJ. 2007. The role of bone morphogenetic protein 4 in inner ear development and function. Hear Res 225(1-2):71-9. [PubMed: 17275231]  [MGI Ref ID J:118380]

Chang B; Hawes NL; Hurd RE; Wang J; Howell D; Davisson MT; Roderick TH; Nusinowitz S; Heckenlively JR. 2005. Mouse models of ocular diseases. Vis Neurosci 22(5):587-93. [PubMed: 16332269]  [MGI Ref ID J:156373]

Chang B; Smith RS; Peters M; Savinova OV; Hawes NL; Zabaleta A; Nusinowitz S; Martin JE; Davisson ML; Cepko CL; Hogan BL; John SW. 2001. Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure. BMC Genet 2(1):18. [PubMed: 11722794]  [MGI Ref ID J:82877]

Chang W; Lin Z; Kulessa H; Hebert J; Hogan BL; Wu DK. 2008. Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet 4(4):e1000050. [PubMed: 18404215]  [MGI Ref ID J:136636]

Dunn NR; Winnier GE; Hargett LK; Schrick JJ; Fogo AB; Hogan BL. 1997. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 188(2):235-47. [PubMed: 9268572]  [MGI Ref ID J:42445]

Fujiwara T; Dehart DB; Sulik KK; Hogan BL. 2002. Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse. Development 129(20):4685-96. [PubMed: 12361961]  [MGI Ref ID J:79391]

Fujiwara T; Dunn NR; Hogan BL. 2001. Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse. Proc Natl Acad Sci U S A 98(24):13739-44. [PubMed: 11707591]  [MGI Ref ID J:72979]

Furuta Y; Hogan BLM. 1998. BMP4 is essential for lens induction in the mouse embryo. Genes Dev 12(23):3764-75. [PubMed: 9851982]  [MGI Ref ID J:51570]

Goncalves A; Zeller R. 2011. Genetic Analysis Reveals an Unexpected Role of BMP7 in Initiation of Ureteric Bud Outgrowth in Mouse Embryos. PLoS One 6(4):e19370. [PubMed: 21552539]  [MGI Ref ID J:172359]

Hu J; Chen YX; Wang D; Qi X; Li TG; Hao J; Mishina Y; Garbers DL; Zhao GQ. 2004. Developmental expression and function of Bmp4 in spermatogenesis and in maintaining epididymal integrity. Dev Biol 276(1):158-71. [PubMed: 15531371]  [MGI Ref ID J:95022]

Jiao K; Kulessa H; Tompkins K; Zhou Y; Batts L; Baldwin HS; Hogan BL. 2003. An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev 17(19):2362-7. [PubMed: 12975322]  [MGI Ref ID J:86001]

Katagiri T; Boorla S; Frendo JL; Hogan BL; Karsenty G. 1998. Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice. Dev Genet 22(4):340-8. [PubMed: 9664686]  [MGI Ref ID J:48538]

Kulessa H; Hogan BL. 2002. Generation of a loxP flanked bmp4(loxP-lacZ) allele marked by conditional lacZ expression. Genesis 32(2):66-8. [PubMed: 11857779]  [MGI Ref ID J:75136]

Lamm ML; Podlasek CA; Barnett DH; Lee J; Clemens JQ; Hebner CM; Bushman W. 2001. Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate. Dev Biol 232(2):301-14. [PubMed: 11401393]  [MGI Ref ID J:69382]

Lawson KA; Dunn NR; Roelen BA; Zeinstra LM; Davis AM; Wright CV ; Korving JP ; Hogan BL. 1999. Bmp4 is required for the generation of primordial germ cells in the mouse embryo [see comments] Genes Dev 13(4):424-36. [PubMed: 10049358]  [MGI Ref ID J:53311]

Miura S; Mishina Y. 2011. Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) is involved in BMP signaling through phosphorylation of smads and TAK1 in early mouse embryo. Dev Dyn 240(11):2474-81. [PubMed: 21953618]  [MGI Ref ID J:177114]

Murali D; Yoshikawa S; Corrigan RR; Plas DJ; Crair MC; Oliver G; Lyons KM; Mishina Y; Furuta Y. 2005. Distinct developmental programs require different levels of Bmp signaling during mouse retinal development. Development 132(5):913-23. [PubMed: 15673568]  [MGI Ref ID J:96964]

Ohinata Y; Ohta H; Shigeta M; Yamanaka K; Wakayama T; Saitou M. 2009. A signaling principle for the specification of the germ cell lineage in mice. Cell 137(3):571-84. [PubMed: 19410550]  [MGI Ref ID J:148768]

Paine-Saunders S; Viviano BL; Zupicich J; Skarnes WC; Saunders S. 2000. glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev Biol 225(1):179-87. [PubMed: 10964473]  [MGI Ref ID J:64330]

Takuma N; Sheng HZ; Furuta Y; Ward JM; Sharma K; Hogan BL; Pfaff SL; Westphal H; Kimura S; Mahon KA. 1998. Formation of Rathke's pouch requires dual induction from the diencephalon. Development 125(23):4835-40. [PubMed: 9806931]  [MGI Ref ID J:50517]

Tominaga T; Abe H; Ueda O; Goto C; Nakahara K; Murakami T; Matsubara T; Mima A; Nagai K; Araoka T; Kishi S; Fukushima N; Jishage K; Doi T. 2011. Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy. J Biol Chem 286(22):20109-16. [PubMed: 21471216]  [MGI Ref ID J:173500]

Uchimura T; Komatsu Y; Tanaka M; McCann KL; Mishina Y. 2009. Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development. Genesis 47(6):374-84. [PubMed: 19391114]  [MGI Ref ID J:149892]

Vervoort R; Ceulemans H; Van Aerschot L; D'Hooge R; David G. 2010. Genetic modification of the inner ear lateral semicircular canal phenotype of the Bmp4 haplo-insufficient mouse. Biochem Biophys Res Commun 394(3):780-5. [PubMed: 20233579]  [MGI Ref ID J:159227]

Wijgerde M; Karp S; McMahon J; McMahon AP. 2005. Noggin antagonism of BMP4 signaling controls development of the axial skeleton in the mouse. Dev Biol 286(1):149-57. [PubMed: 16122729]  [MGI Ref ID J:103548]

Yamaji M; Seki Y; Kurimoto K; Yabuta Y; Yuasa M; Shigeta M; Yamanaka K; Ohinata Y; Saitou M. 2008. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 40(8):1016-22. [PubMed: 18622394]  [MGI Ref ID J:138571]

Ying Y; Liu XM; Marble A; Lawson KA; Zhao GQ. 2000. Requirement of Bmp8b for the generation of primordial germ cells in the mouse Mol Endocrinol 14(7):1053-63. [PubMed: 10894154]  [MGI Ref ID J:63160]

Ying Y; Zhao GQ. 2001. Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 232(2):484-92. [PubMed: 11401407]  [MGI Ref ID J:69376]

Zakin L; De Robertis EM. 2004. Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development. Development 131(2):413-24. [PubMed: 14681194]  [MGI Ref ID J:90398]

de Sousa Lopes SM; Roelen BA; Monteiro RM; Emmens R; Lin HY; Li E; Lawson KA; Mummery CL. 2004. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev 18(15):1838-49. [PubMed: 15289457]  [MGI Ref ID J:91660]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

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Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & HusbandryThe strain is maintained by breeding heterozygous mice to normal wildtype siblings or C57BL/6 inbred mice. Heterozygous breeder pairs are supplied. Female heterozygous mice appear to be poorer breeders than wildtype females and often have an inner ear defect that may cause the mice to spin. Heterozygous breeders are selected for the least severe expression of the inner ear defect. Expected coat color from breeding:Black
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Cryopreserved

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Cryorecovery* $1980.00
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At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

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    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

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Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2574.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

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Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

General Supply Notes

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

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  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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