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; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N21p Generation Definitions   Donating Investigator Gerard Karsenty,   Baylor College of Medicine

Description
Mice homozygous for the null Bmp7 allele die within 48 hours after birth and appear smaller in size when compared to wildtype litter mates. Most display polydactyly in the hindlimbs and exhibit skeletal abnormalities involving the rib cage and skull. Unilateral or bilateral eye defects are present in a majority of the null animals. This defect occurs variably, ranging from a complete absence of eye structures to eyes of normal size. Autopsies on newborn null pups reveal the presence of dysgenic kidneys with hydroureters. Histological examination indicates that homozygous null kidneys possess less than 3 percent of the wildtype number of glomeruli, suggesting that Bmp7 plays a critical role during nephrogenesis. Heterozygous animals appear to display a wildtype phenotype.

Development
A targeting vector containing a hypoxanthine phosphoribosyl transferase gene driven by the mouse phosphoglycerate kinase promoter and a herpes simplex virus thymidine kinase was used to disrupt Bmp7 exons 6 and 7. The construct was transfected into AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Bmp7^tm1Kry/Bmp7^tm1Kry

        Background Not Specified

• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • homozygotes display normal formation of the outflow tract cushions   (MGI Ref ID J:89237)

Bmp7^tm1Kry/Bmp7^tm1Kry

        involves: 129S7/SvEvBrd * C57BL/6

• mortality/aging
• complete postnatal lethality
  • homozygous null mice die within 48 hours after birth   (MGI Ref ID J:30056)
• craniofacial phenotype
• abnormal alisphenoid bone morphology
  • mutants show a fusion between the basisphenoid and the inner ear   (MGI Ref ID J:30056)
• abnormal basisphenoid bone morphology
  • mutants show a fusion between the right alisphenoid and the inner ear   (MGI Ref ID J:30056)
• • basisphenoid bone foramen
    • the basisphenoid bones display a cavity in the center   (MGI Ref ID J:30056)
  • small basisphenoid bone
    • the basisphenoid bones are smaller   (MGI Ref ID J:30056)
• small pterygoid bone
  • mutants show a reduction in the size of the pterygoid bones   (MGI Ref ID J:30056)
• embryogenesis phenotype
• abnormal apical ectodermal ridge morphology
  • the AER is 10-12% longer in mutant limbs than in wild-type limbs, and Fgf8 expression is concomitant with the extended ridge   (MGI Ref ID J:35171)
• broad limb buds
  • consistent with the increase noted in ridge length, the mutant limb buds are broader than those of wild-type mice   (MGI Ref ID J:35171)
• growth/size phenotype
• decreased body size
  • homozygous null mice appear smaller in size relative to wild-type   (MGI Ref ID J:30056)
• • decreased body weight
    • the body weight of homozygous null mice is 85% of wild-type weight   (MGI Ref ID J:30056)
• limbs/digits/tail phenotype
• abnormal apical ectodermal ridge morphology
  • the AER is 10-12% longer in mutant limbs than in wild-type limbs, and Fgf8 expression is concomitant with the extended ridge   (MGI Ref ID J:35171)
• abnormal digit morphology
  • in homozygotes, the cuboideum digit is malformed   (MGI Ref ID J:35171)
  • the relative positions between the cuboideum, the navicular, and the cuneiform I, II, and III have changed to accommodate the presence of the extra digit on the anterior side of the limb   (MGI Ref ID J:35171)
  • in other cases, the cuneiform I is smaller than its duplicate and the metatarsals are fused at their proximal ends   (MGI Ref ID J:35171)
  • the phalanges of the additional anterior digit are slightly longer than those of the first normal digit   (MGI Ref ID J:35171)
• • polydactyly
    • 82% of homozygotes display polydactyly in the hindlimbs   (MGI Ref ID J:30056)
    • 12% of homozygotes display polydactyly in the forelimbs   (MGI Ref ID J:30056)
    • the extra digit is a preaxial duplication, and has the morphology of digit II, III, IV or V   (MGI Ref ID J:30056)
• broad limb buds
  • consistent with the increase noted in ridge length, the mutant limb buds are broader than those of wild-type mice   (MGI Ref ID J:35171)
• renal/urinary system phenotype
• absent metanephric mesenchyme
  • at 14 dpc, dysgenic kidneys lack metanephric mesenchyme   (MGI Ref ID J:30056)
• decreased renal glomerulus number
  • at 14 dpc, dysgenic kidneys show no evidence of glomerulus formation in the cortical region (less than 3% of wild-type glomerular number)   (MGI Ref ID J:30056)
• hydroureter
  • all newborn null pups exhibit dysgenic kidneys with hydroureters   (MGI Ref ID J:30056)
• small kidney
  • all homozygotes have small kidneys   (MGI Ref ID J:30056)
• skeleton phenotype
• *normal* skeleton phenotype
  • homozygotes display no consistent abnormalities in the patterning of the axial skeleton   (MGI Ref ID J:30056)
• • abnormal alisphenoid bone morphology
    • mutants show a fusion between the basisphenoid and the inner ear   (MGI Ref ID J:30056)
  • abnormal basisphenoid bone morphology
    • mutants show a fusion between the right alisphenoid and the inner ear   (MGI Ref ID J:30056)
  • • basisphenoid bone foramen
      • the basisphenoid bones display a cavity in the center   (MGI Ref ID J:30056)
    • small basisphenoid bone
      • the basisphenoid bones are smaller   (MGI Ref ID J:30056)
  • abnormal xiphoid process morphology
    • some mutants display malformation of the xiphoid process   (MGI Ref ID J:30056)
  • asymmetric rib-sternum attachment
    • some mutants show misalignment of the ribs on the sternum   (MGI Ref ID J:30056)
  • decreased rib number
    • some homozygotes display less than 7 pairs of attached ribs, and reduction of one or both of the most posterior pair of ribs   (MGI Ref ID J:30056)
  • rib fusion
    • some homozygotes exhibit rib fusion   (MGI Ref ID J:30056)
  • small pterygoid bone
    • mutants show a reduction in the size of the pterygoid bones   (MGI Ref ID J:30056)
• vision/eye phenotype
• abnormal lens vesicle development
  • at 11.0 dpc, the optic cups and lens vesicles have not formed unilaterally (21%) or bilaterally (14%)   (MGI Ref ID J:30056)
  • in the remaining mutant embryos (65%), optic cups are present and lens formation occurs normally; however, lens vesicles appear smaller relative to wild-type   (MGI Ref ID J:30056)
• anophthalmia
  • most homozygotes exhibit unilateral or bilateral eye defects: this phenotype occurs variably, ranging from a complete absence of eye structures to eyes of normal size   (MGI Ref ID J:30056)
  • 71% of homozygotes show anophthalmia and/or microphthalmia   (MGI Ref ID J:30056)
• aphakia
  • in anophthalmic homozygotes, the lens, retina and cornea are absent; in other mutants, the lens, retina and cornea are well developed   (MGI Ref ID J:30056)

View Research Applications

Research Applications

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

Bmp7^tm1Kry related

Developmental Biology Research
Eye Defects
Internal/Organ Defects
      kidney
Postnatal Lethality
Skeletal Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bmp7tm1Kry
Allele Name		targeted mutation 1, Gerard Karsenty
Allele Type		Targeted (knock-out)
Common Name(s)		Bmp7-; Bmp7delta; bmp-7m1;
Mutation Made By		Gerard Karsenty,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt
ES Cell Line Name		AB2.1
ES Cell Line Strain		129S7/SvEvBrd-Hprt
Gene Symbol and Name		Bmp7, bone morphogenetic protein 7
Chromosome		2
Gene Common Name(s)		BMP-7; OP-1; OP1; osteogenic protein 1;
Molecular Note		An hypoxanthine phosphoribosyl transferase (hprt) minigene replaced a genomic fragment containing exons 6 and 7. These sequences encode the mature domain of the processed polypeptide. Northern blot analysis revealed that no stable transcript was produced from this allele in homozygous mice. [MGI Ref ID J:30056]

Genotyping

Genotyping Information

Genotyping Protocols

Human HPRT Melt Curve Analysis, Melt Curve Analysis
Human HPRT, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Luo G; Hofmann C; Bronckers AL; Sohocki M; Bradley A; Karsenty G. 1995. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 9(22):2808-20. [PubMed: 7590255]  [MGI Ref ID J:30056]

Additional References

Bmp7^tm1Kry related

Benazet JD; Bischofberger M; Tiecke E; Goncalves A; Martin JF; Zuniga A; Naef F; Zeller R. 2009. A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning. Science 323(5917):1050-3. [PubMed: 19229034]  [MGI Ref ID J:144933]

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]

Helder MN; Karg H; Bervoets TJ; Vukicevic S; Burger EH; D'Souza RN; Woltgens JH; Karsenty G; Bronckers AL. 1998. Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development. J Dent Res 77(4):545-54. [PubMed: 9539457]  [MGI Ref ID J:47864]

Hofmann C; Luo G; Balling R; Karsenty G. 1996. Analysis of limb patterning in BMP-7-deficient mice. Dev Genet 19(1):43-50. [PubMed: 8792608]  [MGI Ref ID J:35171]

Ikeya M; Fukushima K; Kawada M; Onishi S; Furuta Y; Yonemura S; Kitamura T; Nosaka T; Sasai Y. 2010. Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors. Dev Biol 337(2):405-14. [PubMed: 19914233]  [MGI Ref ID J:157259]

Ikeya M; Nosaka T; Fukushima K; Kawada M; Furuta Y; Kitamura T; Sasai Y. 2008. Twisted gastrulation mutation suppresses skeletal defect phenotypes in Crossveinless 2 mutant mice. Mech Dev 125(9-10):832-42. [PubMed: 18644438]  [MGI Ref ID J:139028]

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]

Li Y; Litingtung Y; Ten Dijke P; Chiang C. 2007. Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresia. Dev Dyn 236(3):746-54. [PubMed: 17260385]  [MGI Ref ID J:118341]

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]

Ross A; Munger S; Capel B. 2007. Bmp7 regulates germ cell proliferation in mouse fetal gonads. Sex Dev 1(2):127-37. [PubMed: 18391523]  [MGI Ref ID J:137277]

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S7 background and has been backcrossed to C57BL/6 for at least twenty generations. Expected coat color from breeding:Black, Agouti.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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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.

Control Information

	Control
	Wild-type from the colony
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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