Strain Name:

B6;129S-Twist1tm1Bhr/J

Stock Number:

002221

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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

Former Names B6;129S-Twisttm1Bhr    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Richard Behringer,   Univ of Texas, MD Anderson Cancer Center

Description
Homozygotes die at embryonic day 11.5. The most prominent phenotype is a failure of cranial neural tube closure. At embryonic day 8.5 the cranial neural folds are elevated but not fused. At embryonic day 9.5 exencephaly is evident (the cranial neuroepithelium is everted and exposed). There is also abnormal somite morphology and abnormal limb bud development.

Development
This targeted mutant was developed in the Laboratory of Dr. Richard Behringer at the University of Texas, MD Anderson Cancer Center, Houston, Texas. A neo replacement was used that deleted the entire twist protein coding region.

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Twist1tm1Bhr allele
002222   B6.129S7-Twist1tm1Bhr/J
View Strains carrying   Twist1tm1Bhr     (1 strain)

Strains carrying other alleles of Twist1
003821   B6.129S1-Twist1Pde/J
018543   FVB-Tg(CAG-cat,-Twist1)1Dbsp/J
View Strains carrying other alleles of Twist1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Saethre-Chotzen Syndrome; SCS
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Craniosynostosis 1; CRS1   (TWIST1)
Robinow-Sorauf Syndrome   (TWIST1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Twist1tm1Bhr/Twist1+

        involves: 129S7/SvEvBrd * C57BL/6
  • craniofacial phenotype
  • enlarged interparietal bone
    • overdeveloped; 10% larger and 20% longer, on average   (MGI Ref ID J:44379)
  • limbs/digits/tail phenotype
  • polydactyly
    • extra digits found on hindlimbs; usually affecting metatarsus and three phlanges   (MGI Ref ID J:44379)
  • skeleton phenotype
  • enlarged interparietal bone
    • overdeveloped; 10% larger and 20% longer, on average   (MGI Ref ID J:44379)

Twist1tm1Bhr/Twist1+

        involves: 129S/Sv * 129X1/SvJ * C57BL/6
  • skeleton phenotype
  • abnormal osteoblast differentiation
    • at E15 and E16, heterozygous null skulls display a broader zone of mineralized trabeculae in the parietal bone relative to wild-type; osteocalcin is already detectable in the parietal bone and extends toward the midline   (MGI Ref ID J:90056)
    • at P2, mineralized trabeculae have reached the midline suture in heterozygous but not in wild-type skulls; osteocalcin is abnormally detectable on both sides of the suture and reaches the midline, indicating premature osteoblast differentiation   (MGI Ref ID J:90056)
  • premature suture closure
    • in heterozygous null skulls, premature osteoblast differentiation leads to premature suture closure   (MGI Ref ID J:90056)
  • cellular phenotype
  • abnormal osteoblast differentiation
    • at E15 and E16, heterozygous null skulls display a broader zone of mineralized trabeculae in the parietal bone relative to wild-type; osteocalcin is already detectable in the parietal bone and extends toward the midline   (MGI Ref ID J:90056)
    • at P2, mineralized trabeculae have reached the midline suture in heterozygous but not in wild-type skulls; osteocalcin is abnormally detectable on both sides of the suture and reaches the midline, indicating premature osteoblast differentiation   (MGI Ref ID J:90056)

Twist1tm1Bhr/Twist1+

        involves: 129S7/SvEvBrd * C57BL/6J
  • craniofacial phenotype
  • short squamosal bone
    • in all mice at E18.5   (MGI Ref ID J:128714)
  • limbs/digits/tail phenotype
  • polydactyly
    • at E18.5, 10 of 18 mice exhibit hindlimb polydactyly   (MGI Ref ID J:128714)
  • skeleton phenotype
  • short squamosal bone
    • in all mice at E18.5   (MGI Ref ID J:128714)

Twist1tm1Bhr/Twist1tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6
  • mortality/aging
  • complete embryonic lethality
    • die by E11.5   (MGI Ref ID J:24349)
  • nervous system phenotype
  • exencephaly
    • neural tube open from anterior extremity to rhombemere 4   (MGI Ref ID J:24349)
  • open neural tube
    • often accompanied by cranial neural fold hemorrhages; caudal region open, but trunk region often closed   (MGI Ref ID J:24349)
  • embryogenesis phenotype
  • open neural tube
    • often accompanied by cranial neural fold hemorrhages; caudal region open, but trunk region often closed   (MGI Ref ID J:24349)

Twist1tm1Bhr/Twist1tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6J
  • cardiovascular system phenotype
  • internal hemorrhage
    • at E11.5, blood pooling in the cranial region is observed   (MGI Ref ID J:128714)
  • limbs/digits/tail phenotype
  • abnormal forelimb morphology
    • at E11.5, forelimbs are reduced in size compared to wild-type mice   (MGI Ref ID J:128714)
  • nervous system phenotype
  • exencephaly   (MGI Ref ID J:128714)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Twist1tm1Bhr/Twist1+

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • craniofacial phenotype
  • *normal* craniofacial phenotype
    • the overall shape of the neurocranium was normal   (MGI Ref ID J:79294)
    • abnormal temporal bone morphology
      • poorly developed   (MGI Ref ID J:79294)
  • limbs/digits/tail phenotype
  • abnormal limb morphology
    • observed in 71% of mice   (MGI Ref ID J:79294)
  • skeleton phenotype
  • abnormal temporal bone morphology
    • poorly developed   (MGI Ref ID J:79294)
  • premature suture closure
    • cranial suture abnormalities were observed in 89% of mice   (MGI Ref ID J:79294)
    • 68% showed complete or partial craniosynostosis of the occipitointerparietal (OIP) suture   (MGI Ref ID J:79294)
    • 57% showed complete or partial craniosynostosis of the coronal suture   (MGI Ref ID J:79294)

Twist1tm1Bhr/Twist1+

        involves: 129S7/SvEvBrd
  • skeleton phenotype
  • premature suture closure
    • 88% penetrance   (MGI Ref ID J:108218)

Twist1tm1Bhr/Twist1tm1Bhr

        involves: 129S7/SvEvBrd
  • muscle phenotype
  • abnormal muscle development
    • cranial muscle patterning and differentiation are abnormal as determined by marker expression   (MGI Ref ID J:124278)
View Research Applications

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

Twist1tm1Bhr related

Developmental Biology Research
Neural Tube Defects

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Twist1tm1Bhr
Allele Name targeted mutation 1, Richard R Behringer
Allele Type Targeted (knock-out)
Common Name(s) twist-1-; twist1del;
Mutation Made ByDr. Richard Behringer,   Univ of Texas, MD Anderson Cancer Center
Strain of Origin129S7/SvEvBrd-Hprt<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name Twist1, twist basic helix-loop-helix transcription factor 1
Chromosome 12
Gene Common Name(s) AA960487; ACS3; BPES2; BPES3; CRS; CRS1; M-Twist; Pde; Pluridigite; SCS; Ska10; Skam10Jus; TWIST; bHLHa38; charlie chaplin; expressed sequence AA960487; pdt; polydactyly EMS; skeletal/axial 10;
Molecular Note A neomycin selection cassette replaced exon 1, which contains the entire coding region. [MGI Ref ID J:24349]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chen ZF; Behringer RR. 1995. twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev 9(6):686-99. [PubMed: 7729687]  [MGI Ref ID J:24349]

Additional References

Twist1tm1Bhr related

Behr B; Longaker MT; Quarto N. 2010. Differential activation of canonical Wnt signaling determines cranial sutures fate: a novel mechanism for sagittal suture craniosynostosis. Dev Biol 344(2):922-40. [PubMed: 20547147]  [MGI Ref ID J:163650]

Bialek P; Kern B; Yang X; Schrock M; Sosic D; Hong N; Wu H; Yu K; Ornitz DM; Olson EN; Justice MJ; Karsenty G. 2004. A twist code determines the onset of osteoblast differentiation. Dev Cell 6(3):423-35. [PubMed: 15030764]  [MGI Ref ID J:90056]

Bildsoe H; Loebel DA; Jones VJ; Hor AC; Braithwaite AW; Chen YT; Behringer RR; Tam PP. 2013. The mesenchymal architecture of the cranial mesoderm of mouse embryos is disrupted by the loss of Twist1 function. Dev Biol 374(2):295-307. [PubMed: 23261931]  [MGI Ref ID J:193413]

Bourgeois P; Bolcato-Bellemin AL; Danse JM; Bloch-Zupan A; Yoshiba K; Stoetzel C; Perrin-Schmitt F. 1998. The variable expressivity and incomplete penetrance of the twist-null heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome. Hum Mol Genet 7(6):945-57. [PubMed: 9580658]  [MGI Ref ID J:47975]

Carver EA; Oram KF; Gridley T. 2002. Craniosynostosis in Twist heterozygous mice: A model for Saethre-Chotzen syndrome. Anat Rec 268(2):90-2. [PubMed: 12221714]  [MGI Ref ID J:79294]

Chen YT; Akinwunmi PO; Deng JM; Tam OH; Behringer RR. 2007. Generation of a Twist1 conditional null allele in the mouse. Genesis 45(9):588-92. [PubMed: 17868088]  [MGI Ref ID J:128714]

Connerney J; Andreeva V; Leshem Y; Mercado MA; Dowell K; Yang X; Lindner V; Friesel RE; Spicer DB. 2008. Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure. Dev Biol 318(2):323-34. [PubMed: 18471809]  [MGI Ref ID J:136965]

Connerney J; Andreeva V; Leshem Y; Muentener C; Mercado MA; Spicer DB. 2006. Twist1 dimer selection regulates cranial suture patterning and fusion. Dev Dyn 235(5):1334-46. [PubMed: 16502419]  [MGI Ref ID J:108218]

Firulli BA; Krawchuk D; Centonze VE; Vargesson N; Virshup DM; Conway SJ; Cserjesi P; Laufer E; Firulli AB. 2005. Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nat Genet 37(4):373-81. [PubMed: 15735646]  [MGI Ref ID J:105168]

Ishii M; Merrill AE; Chan YS; Gitelman I; Rice DP; Sucov HM; Maxson RE Jr. 2003. Msx2 and Twist cooperatively control the development of the neural crest-derived skeletogenic mesenchyme of the murine skull vault. Development 130(24):6131-42. [PubMed: 14597577]  [MGI Ref ID J:87044]

Krawchuk D; Weiner SJ; Chen YT; Lu BC; Costantini F; Behringer RR; Laufer E. 2010. Twist1 activity thresholds define multiple functions in limb development. Dev Biol 347(1):133-46. [PubMed: 20732316]  [MGI Ref ID J:165721]

Loebel DA; Tsoi B; Wong N; Tam PP. 2005. A conserved noncoding intronic transcript at the mouse Dnm3 locus. Genomics 85(6):782-9. [PubMed: 15885504]  [MGI Ref ID J:99344]

Merrill AE; Bochukova EG; Brugger SM; Ishii M; Pilz DT; Wall SA; Lyons KM; Wilkie AO; Maxson RE Jr. 2006. Cell mixing at a neural crest-mesoderm boundary and deficient ephrin-Eph signaling in the pathogenesis of craniosynostosis. Hum Mol Genet 15(8):1319-28. [PubMed: 16540516]  [MGI Ref ID J:144134]

O'Rourke MP; Soo K; Behringer RR; Hui CC; Tam PP. 2002. Twist plays an essential role in FGF and SHH signal transduction during mouse limb development. Dev Biol 248(1):143-56. [PubMed: 12142027]  [MGI Ref ID J:78407]

Oram KF; Gridley T. 2005. Mutations in Snail Family Genes Enhance Craniosynostosis of Twist1 Haplo-insufficient Mice: Implications for Saethre-Chotzen Syndrome. Genetics 170(2):971-4. [PubMed: 15802514]  [MGI Ref ID J:99331]

Ota MS; Loebel DA; O'Rourke MP; Wong N; Tsoi B; Tam PP. 2004. Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells. Dev Dyn 230(2):216-28. [PubMed: 15162501]  [MGI Ref ID J:90276]

Pan D; Fujimoto M; Lopes A; Wang YX. 2009. Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell 137(1):73-86. [PubMed: 19345188]  [MGI Ref ID J:147973]

Pham D; Vincentz JW; Firulli AB; Kaplan MH. 2012. Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function. J Immunol 189(2):832-40. [PubMed: 22685315]  [MGI Ref ID J:189552]

Rice DP; Aberg T; Chan Y; Tang Z; Kettunen PJ; Pakarinen L; Maxson RE; Thesleff I. 2000. Integration of FGF and TWIST in calvarial bone and suture development. Development 127(9):1845-55. [PubMed: 10751173]  [MGI Ref ID J:61430]

Rinon A; Lazar S; Marshall H; Buchmann-Moller S; Neufeld A; Elhanany-Tamir H; Taketo MM; Sommer L; Krumlauf R; Tzahor E. 2007. Cranial neural crest cells regulate head muscle patterning and differentiation during vertebrate embryogenesis. Development 134(17):3065-75. [PubMed: 17652354]  [MGI Ref ID J:124278]

Sharif MN; Sosic D; Rothlin CV; Kelly E; Lemke G; Olson EN; Ivashkiv LB. 2006. Twist mediates suppression of inflammation by type I IFNs and Axl. J Exp Med 203(8):1891-901. [PubMed: 16831897]  [MGI Ref ID J:124396]

Sharma VP; Fenwick AL; Brockop MS; McGowan SJ; Goos JA; Hoogeboom AJ; Brady AF; Jeelani NO; Lynch SA; Mulliken JB; Murray DJ; Phipps JM; Sweeney E; Tomkins SE; Wilson LC; Bennett S; Cornall RJ; Broxholme J; Kanapin A; Johnson D; Wall SA; van der Spek PJ;Mathijssen IM; Maxson RE; Twigg SR; Wilkie AO. 2013. Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nat Genet 45(3):304-7. [PubMed: 23354436]  [MGI Ref ID J:198060]

Soo K; O'Rourke MP; Khoo PL; Steiner KA; Wong N; Behringer RR; Tam PP. 2002. Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo. Dev Biol 247(2):251-70. [PubMed: 12086465]  [MGI Ref ID J:77801]

Sosic D; Richardson JA; Yu K; Ornitz DM; Olson EN. 2003. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity. Cell 112(2):169-80. [PubMed: 12553906]  [MGI Ref ID J:81485]

Ting MC; Wu NL; Roybal PG; Sun J; Liu L; Yen Y; Maxson RE Jr. 2009. EphA4 as an effector of Twist1 in the guidance of osteogenic precursor cells during calvarial bone growth and in craniosynostosis. Development 136(5):855-64. [PubMed: 19201948]  [MGI Ref ID J:146459]

Vincentz JW; Barnes RM; Rodgers R; Firulli BA; Conway SJ; Firulli AB. 2008. An absence of Twist1 results in aberrant cardiac neural crest morphogenesis. Dev Biol 320(1):131-9. [PubMed: 18539270]  [MGI Ref ID J:138404]

Vincentz JW; Firulli BA; Lin A; Spicer DB; Howard MJ; Firulli AB. 2013. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest. PLoS Genet 9(3):e1003405. [PubMed: 23555309]  [MGI Ref ID J:195264]

Vrljicak P; Cullum R; Xu E; Chang AC; Wederell ED; Bilenky M; Jones SJ; Marra MA; Karsan A; Hoodless PA. 2012. Twist1 transcriptional targets in the developing atrio-ventricular canal of the mouse. PLoS One 7(7):e40815. [PubMed: 22815831]  [MGI Ref ID J:189611]

Yen HY; Ting MC; Maxson RE. 2010. Jagged1 functions downstream of Twist1 in the specification of the coronal suture and the formation of a boundary between osteogenic and non-osteogenic cells. Dev Biol 347(2):258-70. [PubMed: 20727876]  [MGI Ref ID J:166632]

el Ghouzzi V; Le Merrer M; Perrin-Schmitt F; Lajeunie E; Benit P; Renier D; Bourgeois P; Bolcato-Bellemin AL; Munnich A; Bonaventure J. 1997. Mutations of the TWIST gene in the Saethre-Chotzen syndrome [see comments] Nat Genet 15(1):42-6. [PubMed: 8988167]  [MGI Ref ID J:44379]

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, G200.

Colony Maintenance

Breeding & HusbandryThis strain is maintained by heterozygous matings as the homozygotes die in utero.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3175.00
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 on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4127.50
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 on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   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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