Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   12-NOV-12 Species laboratory mouse Generation F?pN1+F3 (12-MAR-13) Generation Definitions   Donating Investigator James F Martin,   Baylor College of Medicine

Description
Mice homozygous for this Bmp4^floxneo allele have loxP sites flanking exon 4 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the endogenous mature peptide deleted in the cre-expressing tissues resulting in a null allele. Mice homozygous for the Bmp4^floxneo allele are viable and fertile. These mutant mice may be useful in generating conditional mutations for studying the role of Bmp4 in bone morphogenetic protein signaling pathways, bone biology, cardiovascular biology, and cancer (Bmp4 misregulation is associated with cancer cell motility/invasiveness and epithelial-to-mesenchymal transition/transformation [EMT]).

For example, when crossed to a strain expressing Cre recombinase in early limb bud mesenchyme and in a subset of craniofacial mesenchyme (see Stock No. 005584), this mutant mouse strain may be useful in studies of limb patterning and skeletogenesis.

Development
A targeting vector was designed to insert a loxP site upstream of exon 4, and a second loxP site followed by an frt-flanked PGK-neo cassette just downstream of exon 4 of the targeted gene. The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6 females to establish the colony. Mice heterozygous for the Bmp4^floxneo allele were bred together to generate homozygotes prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Bmp4

002612

B6.129S2-Bmp4tm1Blh/J

View Strains carrying other alleles of Bmp4     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Microphthalmia, Syndromic 6; MCOPS6   (BMP4) Orofacial Cleft 11; OFC11   (BMP4)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Bmp4^tm1Jfm/Bmp4^tm1.1Jfm Tg(Prrx1-cre)1Cjt/0

        involves: 129S4/SvJaeSor   (conditional)

• cardiovascular system phenotype
• conotruncal ridge hypoplasia
  • severely reduced outflow tract cushions, which developed into a shortened outflow tract   (MGI Ref ID J:89237)

Bmp4^tm1Jfm/Bmp4^tm1Jfm Tg(Prrx1-cre)1Cjt/0

        involves: 129S4/SvJaeSor * C57BL/6 * SJL   (conditional)

• limbs/digits/tail phenotype
• polydactyly
  • mice exhibit variable penetrance of preaxial and postaxial polydactyly, however exhibit normal digit patterns   (MGI Ref ID J:118257)

View Research Applications

Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines
Increased Tumor Incidence
Other
      tumor metastasis
Tumor Suppressor Genes

Cardiovascular Research
Other

Cell Biology Research
Signal Transduction

Developmental Biology Research
Cell Motility Defects
Defects in Cell Adhesion Molecules
Mesodermal Defects
Skeletal Defects

Internal/Organ Research
Skeleton
      Bone

Research Tools
Cancer Research
      anti-tumor activity
      tumor immunology
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
      Tissue/Cell Markers: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bmp4tm1Jfm
Allele Name		targeted mutation 1, James F Martin
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Bmp4clc; Bmp4floxneo;
Mutation Made By		James Martin,   Baylor College of Medicine
Strain of Origin		129S4/SvJaeSor
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 loxP site was introduced upstream of exon 4 and another loxP site followed by a FRT-flanked neo was inserted downstream of exon 4. PCR was used to confirm recombination. [MGI Ref ID J:89237]

Genotyping

Genotyping Information

Genotyping Protocols

Bmp4^tm1Jfm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liu W; Selever J; Wang D; Lu MF; Moses KA; Schwartz RJ; Martin JF. 2004. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A 101(13):4489-94. [PubMed: 15070745]  [MGI Ref ID J:89237]

Wang J; Greene SB; Bonilla-Claudio M; Tao Y; Zhang J; Bai Y; Huang Z; Black BL; Wang F; Martin JF. 2010. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell 19(6):903-12. [PubMed: 21145505]  [MGI Ref ID J:169047]

Additional References

Bmp4^tm1Jfm related

Bandyopadhyay A; Tsuji K; Cox K; Harfe BD; Rosen V; Tabin CJ. 2006. Genetic Analysis of the Roles of BMP2, BMP4, and BMP7 in Limb Patterning and Skeletogenesis. PLoS Genet 2(12):e216. [PubMed: 17194222]  [MGI Ref ID J:118257]

Benazet JD; Pignatti E; Nugent A; Unal E; Laurent F; Zeller R. 2012. Smad4 is required to induce digit ray primordia and to initiate the aggregation and differentiation of chondrogenic progenitors in mouse limb buds. Development 139(22):4250-60. [PubMed: 23034633]  [MGI Ref ID J:189073]

Blitz E; Viukov S; Sharir A; Shwartz Y; Galloway JL; Pryce BA; Johnson RL; Tabin CJ; Schweitzer R; Zelzer E. 2009. Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell 17(6):861-73. [PubMed: 20059955]  [MGI Ref ID J:156015]

Bonilla-Claudio M; Wang J; Bai Y; Klysik E; Selever J; Martin JF. 2012. Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development. Development 139(4):709-19. [PubMed: 22219353]  [MGI Ref ID J:181229]

Jain R; Engleka KA; Rentschler SL; Manderfield LJ; Li L; Yuan L; Epstein JA. 2011. Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J Clin Invest 121(1):422-30. [PubMed: 21157040]  [MGI Ref ID J:171842]

Jia S; Zhou J; Gao Y; Baek JA; Martin JF; Lan Y; Jiang R. 2013. Roles of Bmp4 during tooth morphogenesis and sequential tooth formation. Development 140(2):423-32. [PubMed: 23250216]  [MGI Ref ID J:191714]

Klaus A; Muller M; Schulz H; Saga Y; Martin JF; Birchmeier W. 2012. Wnt/beta-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells. Proc Natl Acad Sci U S A 109(27):10921-6. [PubMed: 22711842]  [MGI Ref ID J:186421]

Liu W; Selever J; Murali D; Sun X; Brugger SM; Ma L; Schwartz RJ; Maxson R; Furuta Y; Martin JF. 2005. Threshold-specific requirements for Bmp4 in mandibular development. Dev Biol 283(2):282-93. [PubMed: 15936012]  [MGI Ref ID J:99697]

Liu W; Sun X; Braut A; Mishina Y; Behringer RR; Mina M; Martin JF. 2005. Distinct functions for Bmp signaling in lip and palate fusion in mice. Development 132(6):1453-61. [PubMed: 15716346]  [MGI Ref ID J:97214]

Lopez-Rios J; Speziale D; Robay D; Scotti M; Osterwalder M; Nusspaumer G; Galli A; Hollander GA; Kmita M; Zeller R. 2012. GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis. Dev Cell 22(4):837-48. [PubMed: 22465667]  [MGI Ref ID J:184012]

Maatouk DM; Choi KS; Bouldin CM; Harfe BD. 2009. In the limb AER Bmp2 and Bmp4 are required for dorsal-ventral patterning and interdigital cell death but not limb outgrowth. Dev Biol 327(2):516-23. [PubMed: 19210962]  [MGI Ref ID J:146434]

McCulley DJ; Kang JO; Martin JF; Black BL. 2008. BMP4 is required in the anterior heart field and its derivatives for endocardial cushion remodeling, outflow tract septation, and semilunar valve development. Dev Dyn 237(11):3200-9. [PubMed: 18924235]  [MGI Ref ID J:140658]

Rock JR; Cecilia Lopez M; Baker HV; Harfe BD. 2007. Identification of genes expressed in the mouse limb using a novel ZPA microarray approach. Gene Expr Patterns 8(1):19-26. [PubMed: 17911046]  [MGI Ref ID J:127128]

Selever J; Liu W; Lu MF; Behringer RR; Martin JF. 2004. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev Biol 276(2):268-79. [PubMed: 15581864]  [MGI Ref ID J:128571]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   12-NOV-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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