Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129S2 via D3 ES cell line Generation N22p (13-FEB-05)   Donating Investigator Brigid Hogan,   Duke University Medical Center

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Bmp4^tm1Blh 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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Axenfeld-Rieger Anomaly with Cardiac Defects and Sensorineural Hearing Loss - 5

5 Conditionally targeted allele(s)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Bmp4^tm1Blh/Bmp4⁺

        B6.129S2-Bmp4^tm1Blh/J

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:42445)
  • less than half as many heterozygotes are born as expected
• vision/eye phenotype
• abnormal eye electrophysiology (MGI Ref ID J:82877)
  • 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
• abnormal eye morphology (MGI Ref ID J:82877)
  • 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
• abnormal anterior eye segment morphology (MGI Ref ID J:82877)
  • variable anterior segment abnormalities in mutants 3-5 months of age
• abnormal cornea morphology (MGI Ref ID J:82877)
  • extracellular matrix (ECM) abnormalities are seen in the peripheral cornea, showing irregularly arranged collagen bundles
• corneal adhesion to iris (MGI Ref ID J:82877)
  • abnormal iridocorneal attachments (anterior synechiae) of variable extent
• corneal opacity (MGI Ref ID J:82877)
  • some eyes exhibit scleralization (opacity) of the the peripheral cornea or diffuse corneal haze
• corneal thinning (MGI Ref ID J:82877)
  • peripheral cornea is often thinner with neovascularization
• abnormal iridocorneal angle (MGI Ref ID J:82877)
  • abnormal in most eyes
• abnormal canal of Schlemm morphology (MGI Ref ID J:82877)
  • small or absent
• absent Schlemm's canal (MGI Ref ID J:82877)
  • small or absent
• abnormal line of Schwalbe (MGI Ref ID J:82877)
  • displaced Schwalbe's line
• absent trabecular meshwork (MGI Ref ID J:82877)
  • hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
• hypoplastic trabecular meshwork (MGI Ref ID J:82877)
  • hypoplastic or absent trabecular meshwork that appears compressed and stalled in development
• abnormal placement of pupils (MGI Ref ID J:82877)
  • pupils are often eccentrically located
• cataracts (MGI Ref ID J:82877)
  • anterior subcapsular and cortical contaracts occur in most mutants
• iris hypoplasia (MGI Ref ID J:82877)
  • 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
• irregularly shaped pupil (MGI Ref ID J:82877)
• abnormal eye size (MGI Ref ID J:42445)
• anophthalmia (MGI Ref ID J:42445)
  • frequency increased 3 fold
• microphthalmia (MGI Ref ID J:42445)
  • frequency increased 3 fold
• abnormal posterior eye segment morphology (MGI Ref ID J:82877)
  • variable posterior eye segment abnormalities
• abnormal optic nerve morphology (MGI Ref ID J:82877)
  • abnormalities of the optic nerve head are frequently observed
  • optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
• absent optic nerve (MGI Ref ID J:82877)
  • the optic nerve is sometimes absent
• abnormal retina morphology (MGI Ref ID J:82877)
• abnormal retinal photoreceptor layer (MGI Ref ID J:82877)
  • photoreceptor layer typically appears normal, however there are foci of retinal dysplasia, characterized by rosette formation
• abnormal retinal vasculature (MGI Ref ID J:82877)
  • the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
• retinal detachment (MGI Ref ID J:82877)
  • about 25% of heterozygotes exhibit retinal detachment as early as P30, with increased incidence as mice age
• thin retinal ganglion layer (MGI Ref ID J:82877)
  • retinal ganglion cell layer on average contains about 50% the normal number of cells
• thin retinal inner nuclear layer (MGI Ref ID J:82877)
• abnormal vitreous body (MGI Ref ID J:82877)
  • dense network of small tortuous vessels throughout the vitreous that leak fluorescein, indicating compromised integrity of the vessels
• opacity of vitreous body (MGI Ref ID J:82877)
  • irregular white patches in the vitreous and dense vitreous haze in the majority of eyes
• persistence of hyaloid capillary system (MGI Ref ID J:82877)
  • 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
• ocular hypertension (MGI Ref ID J:82877)
  • mutants with severe drainage structure abnormalities over 80% or more of their angle's extent have elevated intraocular pressure
• hearing/vestibular/ear phenotype
• abnormal organ of Corti (MGI Ref ID J:118380)
  • 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
• abnormal vestibulocollic reflex (MGI Ref ID J:118380)
  • 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
• circling (MGI Ref ID J:118380)
  • 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
• decreased brainstem auditory evoked potential (MGI Ref ID J:118380)
  • 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
• decreased vestibular hair cell stereocilia number (MGI Ref ID J:118380)
  • 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
• impaired hearing (MGI Ref ID J:118380)
  • both circling and non-circling heterozygotes display a partial hearing loss, as assessed by ABR testing
• nervous system phenotype
• abnormal optic nerve morphology (MGI Ref ID J:82877)
  • abnormalities of the optic nerve head are frequently observed
  • optic nerve abnormalities range from normal to absent, and are most often severely abnormal consisting of loose connective tissue, with absence of neural tissue
• absent optic nerve (MGI Ref ID J:82877)
  • the optic nerve is sometimes absent
• abnormal sensory neuron innervation (MGI Ref ID J:118380)
  • neuronal processes innervating the cochlea of both circling and non-circling heterozygotes mice are reduced in number
• decreased vestibular hair cell stereocilia number (MGI Ref ID J:118380)
  • 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
• behavior/neurological phenotype
• abnormal vestibulocollic reflex (MGI Ref ID J:118380)
  • 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
• circling (MGI Ref ID J:118380)
  • 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
• reproductive system phenotype
• abnormal fertility/fecundity (MGI Ref ID J:118380)
• decreased litter size (MGI Ref ID J:118380)
  • average litter from mating a wild-type C57BL/6 mouse with a C57BL/6 heterozygote yields only 1 heterozygous pup
• reduced female fertility (MGI Ref ID J:118380)
  • female heterozygotes are poorer breeders relative to wild-type females
• abnormal male reproductive anatomy (MGI Ref ID J:42445)
• abnormal coagulating gland morphology (MGI Ref ID J:42445)
  • sometimes cystic
  • sometimes with abnormal lobulation
• abnormal seminiferous tubule morphology (MGI Ref ID J:42445)
  • sometimes cystic
• cardiovascular system phenotype
• abnormal retinal vasculature (MGI Ref ID J:82877)
  • the main retinal vessels branch close to the optic nerve and are irregularly arranged compared to wild-type
• renal/urinary system phenotype
• hydronephrosis (MGI Ref ID J:42445)
  • marked hydronephrosis in 12% of heterozygotes but ureter is undilated
• kidney atrophy (MGI Ref ID J:42445)
  • cortex of remaining kidney is atrophic
• kidney cysts (MGI Ref ID J:42445)
  • single cystic kidney in about 12% of heterozygotes
  • multiple cysts involving both tubules and glomeruli
• single kidney (MGI Ref ID J:42445)
  • single cystic kidney in about 12% of heterozygotes
• craniofacial phenotype
• short frontal bone (MGI Ref ID J:42445)
  • in about 12% of individuals
• short nasal bone (MGI Ref ID J:42445)
  • in about 12% of individuals
• limbs/digits/tail phenotype
• polydactyly (MGI Ref ID J:42445)
  • 12% with unilateral anterior polydactyly involving the right hind limb only
• skeleton phenotype
• short frontal bone (MGI Ref ID J:42445)
  • in about 12% of individuals
• short nasal bone (MGI Ref ID J:42445)
  • in about 12% of individuals
• endocrine/exocrine gland phenotype
• abnormal coagulating gland morphology (MGI Ref ID J:42445)
  • sometimes cystic
  • sometimes with abnormal lobulation
• abnormal seminiferous tubule morphology (MGI Ref ID J:42445)
  • sometimes cystic

Bmp4^tm1Blh/Bmp4^tm1Blh

        B6.129S2-Bmp4^tm1Blh/J

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

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

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * C57BL/6 * CBA

• reproductive system phenotype
• decreased primordial germ cell number (MGI Ref ID J:53311)
  • fewer PGCs due to a reduced founder population rather than impaired expansion
  • estimated 62% reduction in PGC founder population of mice on the C57BL/6, CBA mixed background
  • PGCs were absent in 9% of mutant mice on the C57BL/6, CBA mixed background

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * C3Hf/HeA * C57BL/LiA

• vision/eye phenotype
• abnormal anterior eye segment morphology (MGI Ref ID J:82877)
  • 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
• abnormal iridocorneal angle (MGI Ref ID J:82877)
  • buphthalmos
• large pupils (MGI Ref ID J:82877)
  • 5 of 13 mutants exhibit enlarged pupils

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * CAST/Ei

• vision/eye phenotype
• cataracts (MGI Ref ID J:82877)
  • 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

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * 129S6/SvEvTac

• vision/eye phenotype
• abnormal eye morphology (MGI Ref ID J:82877)
  • 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
• abnormal iris morphology (MGI Ref ID J:82877)
  • 1 of 12 mice shows persistent vitreous vessels
• persistence of hyaloid capillary system (MGI Ref ID J:82877)
  • 1 of 12 mice shows abnormal pupil/iris
• reproductive system phenotype
• decreased primordial germ cell number (MGI Ref ID J:53311)
  • 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

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * BALB/cJ

• vision/eye phenotype
• persistence of hyaloid capillary system (MGI Ref ID J:82877)
  • 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

Bmp4^tm1Blh/Bmp4⁺

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss

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

Bmp4^tm1Blh/Bmp4^tm1Blh

        involves: 129S2/SvPas * Black Swiss

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:51570)
  • at E10.5
• 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
• vision/eye phenotype
• abnormal lens induction (MGI Ref ID J:51570)
  • failure of lens placode induction
• embryogenesis phenotype
• absent allantois (MGI Ref ID J:53311)
  • all embryos lacked an allantois
• embryonic growth retardation (MGI Ref ID J:53311)
  • at E10.5, homozygotes have 20-27 somites, while littermates have greater than 35
• reproductive system phenotype
• absent primordial germ cells (MGI Ref ID J:53311)
• endocrine/exocrine gland phenotype
• abnormal Rathke's pouch (MGI Ref ID J:50517)
  • no thickened ectodermal placode precursor ever forms
• nervous system phenotype
• abnormal Rathke's pouch (MGI Ref ID J:50517)
  • no thickened ectodermal placode precursor ever forms

Bmp4^tm1Blh/Bmp4^tm1Blh

        involves: 129S2/SvPas * C57BL/6

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

Bmp4^tm1Blh/Bmp4^tm1Blh

        129S2/SvPas-Bmp4^tm1Blh

• lethality-prenatal/perinatal
• embryonic lethality before turning of embryo (MGI Ref ID J:28717)
  • none survive beyond the egg cylinder stage
• embryogenesis phenotype
• abnormal extraembryonic tissue morphology (MGI Ref ID J:28717)
  • hypoplastic extraembryonic mesoderm: small amount can be distinguished
• abnormal yolk sac morphology (MGI Ref ID J:28717)
• absent blood islands (MGI Ref ID J:28717)
• failure of primitive streak formation (MGI Ref ID J:28717)
  • absence of organized primitive streak

Bmp4^tm1Blh/Bmp4^tm1Blh

        involves: 129S2/SvPas * ICR

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:28717)
  • embryos die between E9.5-E11.5
• growth/size phenotype
• embryonic growth retardation (MGI Ref ID J:28717)
  • are grossly retarded but have undergone turning, have a beating heart and forelimb buds
• embryogenesis phenotype
• embryonic growth retardation (MGI Ref ID J:28717)
  • are grossly retarded but have undergone turning, have a beating heart and forelimb buds

Bmp4^tm1Blh/Bmp4^tm1Blh

        involves: 129S2/SvPas * C57BL/6 * CBA

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:53311)
• embryogenesis phenotype
• absent allantois (MGI Ref ID J:53311)
  • all embryos lacked an allantois
• embryonic growth retardation (MGI Ref ID J:53311)
• reproductive system phenotype
• absent primordial germ cells (MGI Ref ID J:53311)
  • absent primordial germ cells
• growth/size phenotype
• embryonic growth retardation (MGI Ref ID J:53311)

Bmp4^tm1Blh/Bmp4^tm1Blh

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss

• embryogenesis phenotype
• abnormal left-right axis patterning (MGI Ref ID J:79391)
  • 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
• abnormal mesoderm development (MGI Ref ID J:79391)
  • a mass of mesodermal cells extending to the apical surface of the ectoderm fills much of the posterior amniotic cavity
• abnormal primitive streak morphology (MGI Ref ID J:79391)
  • an abnormal posterior bulge is present from the headfold to 6 somite stage
• abnormal Henson's node morphology (MGI Ref ID J:79391)
  • 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
• cardiovascular system phenotype
• abnormal looping morphogenesis (MGI Ref ID J:79391)
  • 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

Bmp4^tm1Blh/Bmp4^tm4Blh

        involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL

• hearing/vestibular/ear phenotype
• abnormal semicircular canal (MGI Ref ID J:136636)
  • percentage of mice display lateral canal truncation

View Research Applications

Research Applications

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

Bmp4^tm1Blh 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

Allele Symbol		Bmp4tm1Blh
Allele Name		targeted mutation 1, Brigid L Hogan
Allele Type		Targeted (knock-out)
Common Name(s)		Bmp-4tm1blh; Bmp4-; Bmp4tm1;
Mutation Made By		Brigid Hogan,   Duke University Medical Center
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Bmp4, bone morphogenetic protein 4
Chromosome		14
Gene Common Name(s)		BMP2B; BMP2B1; BOMPR4A; Bmp2b; Bmp2b-1; Bmp2b1; MCOPS6; 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

Bmp4^tm1Blh, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

Bmp4^tm1Blh 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; 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]

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]

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]

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]

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; 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

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry

The 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

Diet Information

LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.