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. Species laboratory mouse Generation ?pN1   Donating Investigator 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   Twist1^tm1Bhr allele

002222

B6.129S7-Twist1tm1Bhr/J

View Strains carrying   Twist1^tm1Bhr     (1 strain)

Strains carrying other alleles of Twist1

003821

B6.129S1-Twist1Pde/J

View Strains carrying other alleles of Twist1     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Saethre-Chotzen Syndrome; SCS - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Twist1^tm1Bhr/Twist1⁺

        involves: 129S7/SvEvBrd * C57BL/6

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

Twist1^tm1Bhr/Twist1⁺

        involves: 129S/Sv * C57BL/6

• skeleton phenotype
• abnormal osteoblast differentiation (MGI Ref ID J:90056)
  • 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
  • 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
• premature suture closure (MGI Ref ID J:90056)
  • in heterozygous null skulls, premature osteoblast differentiation leads to premature suture closure

Twist1^tm1Bhr/Twist1⁺

        involves: 129S7/SvEvBrd * C57BL/6J

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

Twist1^tm1Bhr/Twist1^tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:24349)
  • animals die by E11.5
• nervous system phenotype
• exencephaly (MGI Ref ID J:24349)
  • neural tube open from anterior extremity to rhombemere 4
• open neural tube (MGI Ref ID J:24349)
  • often accompanied by cranial neural fold hemorrhages; caudal region open, but trunk region often closed

Twist1^tm1Bhr/Twist1^tm1Bhr

        involves: 129S7/SvEvBrd * C57BL/6J

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

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

Twist1^tm1Bhr/Twist1⁺

        involves: 129S1/Sv * C57BL/6J

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

Twist1^tm1Bhr/Twist1^tm1Bhr

        involves: 129S7/SvEvBrd

• muscle phenotype
• abnormal muscle development (MGI Ref ID J:124278)
  • cranial muscle patterning and differentiation are abnormal as determined by marker expression

View Research Applications

Research Applications

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

Twist1^tm1Bhr related

Developmental Biology Research
Neural Tube Defects

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Twist1tm1Bhr
Allele Name		targeted mutation 1, Richard R Behringer
Allele Type		Targeted (knock-out)
Common Name(s)		twist-1-;
Mutation Made By		Richard Behringer,   Univ of Texas, MD Anderson Cancer Center
Strain of Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		Twist1, twist gene homolog 1 (Drosophila)
Chromosome		12
Gene Common Name(s)		AA960487; ACS3; BPES2; BPES3; 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

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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

Twist1^tm1Bhr related

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]

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]

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]

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]

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]

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]

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]

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

Colony Maintenance

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

Purchasing information

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

Pricing

Supply Details

Standard Supply

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

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
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.

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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

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

JAX^® Mice & Services Conditions of Use

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