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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 Background Strain C57BL/6J Donating Investigator Thomas Doetschman, University of Arizona Description
Mice homozygous for the Tgfb3tm1Doe mutation are not viable. Mice exhibit cleft palate and possibly developmental defects in the lung.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Facebase: models
View Facebase: models (58 strains)
Strains carrying other alleles of Tgfb3
012719 STOCK Tgfb3tm1(cre)Vk/J View Strains carrying other alleles of Tgfb3 (1 strain)
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. Arrhythmogenic Right Ventricular Dysplasia, Familial, 1; ARVD1 (TGFB3)
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.
Tgfb3tm1Doe/Tgfb3+
involves: 129P2/OlaHsd
- digestive/alimentary phenotype
- abnormal enterocyte apoptosis
- abnormal small intestinal villus morphology
- villus length is increased compared to in wild-type mice (MGI Ref ID J:76342)
- cellular phenotype
- abnormal enterocyte apoptosis
Tgfb3tm1Doe/Tgfb3tm1Doe
either: (involves: 129/Sv * 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * CF-1)
- mortality/aging
- complete neonatal lethality
- behavior/neurological phenotype
- absent gastric milk in neonates
- homozygous mutant pups fail to suckle, as shown by absence of milk in their stomachs (MGI Ref ID J:29901)
- craniofacial phenotype
- cleft palate
- newborn homozygotes show a cleft palate phenotype of variable severity and type (anterior vs posterior) that is most severe on a C57BL/6-enriched background (MGI Ref ID J:29901)
- no associated cleft lip or gross abnormalities in cartilage, bone, brain, heart or other craniofacial structures (e.g. mandible) are observed (MGI Ref ID J:29901)
- on a 129P2/OlaHsd x C57BL/6 background, 46.7% of homozygotes exhibit a complete cleft palate while 53.3% display only a posterior cleft (MGI Ref ID J:29901)
- on a 129P2/OlaHsd x CF1 background, 89.3% homozygotes show a posterior cleft palate, 8.7% show anterior clefts (i.e. failure of fusion of primary and secondary palates), and ~2% exhibit complete clefts (MGI Ref ID J:29901)
- on a 129/Sv x 129P2/OlaHsd background, all homozygotes show only a posterior cleft palate (MGI Ref ID J:29901)
- persistence of medial edge epithelium during palatal shelf fusion
- homeostasis/metabolism phenotype
- cyanosis
- newborn pups become cyanotic shortly after birth (MGI Ref ID J:29901)
- dehydration
- newborn pups become dehydrated shortly after birth (MGI Ref ID J:29901)
- respiratory system phenotype
- abnormal respiratory conducting tube morphology
- newborn homozygotes display an abnormal terminal airway system (MGI Ref ID J:29901)
- respiratory distress
- newborn pups exhibit gasping at ~4 hrs after birth (MGI Ref ID J:29901)
- digestive/alimentary phenotype
- cleft palate
- newborn homozygotes show a cleft palate phenotype of variable severity and type (anterior vs posterior) that is most severe on a C57BL/6-enriched background (MGI Ref ID J:29901)
- no associated cleft lip or gross abnormalities in cartilage, bone, brain, heart or other craniofacial structures (e.g. mandible) are observed (MGI Ref ID J:29901)
- on a 129P2/OlaHsd x C57BL/6 background, 46.7% of homozygotes exhibit a complete cleft palate while 53.3% display only a posterior cleft (MGI Ref ID J:29901)
- on a 129P2/OlaHsd x CF1 background, 89.3% homozygotes show a posterior cleft palate, 8.7% show anterior clefts (i.e. failure of fusion of primary and secondary palates), and ~2% exhibit complete clefts (MGI Ref ID J:29901)
- on a 129/Sv x 129P2/OlaHsd background, all homozygotes show only a posterior cleft palate (MGI Ref ID J:29901)
- persistence of medial edge epithelium during palatal shelf fusion
Tgfb3tm1Doe/Tgfb3tm1Doe
involves: 129P2/OlaHsd * C57BL/6
- nervous system phenotype
- decreased neuron apoptosis
- 2-fold in neurons of the substantia nigra pars compacta and ventral tegmental area (MGI Ref ID J:117465)
- loss of dopaminergic neurons
- at P0 in the substantia nigra pars compacta and ventral tegmental area (MGI Ref ID J:117465)
- cellular phenotype
- decreased neuron apoptosis
- 2-fold in neurons of the substantia nigra pars compacta and ventral tegmental area (MGI Ref ID J:117465)
Tgfb3tm1Doe/Tgfb3tm1Doe
involves: 129 * C57BL/6J * ICR * Swiss WebsterView Research Applications
Research Applications
This mouse can be used to support research in many areas including:Tgfb3tm1Doe related
Cancer Research
Growth Factors/Receptors/Cytokines
Developmental Biology Research
Craniofacial and Palate Defects
congenital cleft palate
Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Inflammation
Internal/Organ Research
Lung Defects
| Allele Symbol | Tgfb3tm1Doe | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Thomas Doetschman | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | TGF-beta3 null; | ||
| Mutation Made By | Thomas Doetschman, University of Arizona | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14.1 | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Tgfb3, transforming growth factor, beta 3 | ||
| Chromosome | 12 | ||
| Gene Common Name(s) | ARVD; TGF-beta3; Tgfb-3; | ||
| Molecular Note | A neomycin resistance cassette replaced exon 6, which encodes the active domain of the protein. RT-PCR analysis of RNA derived from whole E11.5 or E15.5 embryos did not detect any transcript produced from this allele in homozygous mice. [MGI Ref ID J:29901] | ||
Genotyping Protocols
Tgfb3tm1Doe, Separated PCR
NEOTD (Generic Neo), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Proetzel G; Pawlowski SA; Wiles MV; Yin M; Boivin GP; Howles PN; Ding J; Ferguson MW; Doetschman T. 1995. Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet 11(4):409-14. [PubMed: 7493021] [MGI Ref ID J:29901]
Cui XM; Chai Y; Chen J; Yamamoto T; Ito Y; Bringas P; Shuler CF. 2003. TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion. Dev Dyn 227(3):387-94. [PubMed: 12815624] [MGI Ref ID J:84447]
Martinez-Alvarez C; Blanco MJ; Perez R; Rabadan MA; Aparicio M; Resel E; Martinez T; Nieto MA. 2004. Snail family members and cell survival in physiological and pathological cleft palates. Dev Biol 265(1):207-18. [PubMed: 14697364] [MGI Ref ID J:87413]
Taya Y; O'Kane S; Ferguson MW. 1999. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development 126(17):3869-79. [PubMed: 10433915] [MGI Ref ID J:56561]
Tgfb3tm1Doe relatedAzhar M; Runyan RB; Gard C; Sanford LP; Miller ML; Andringa A; Pawlowski S; Rajan S; Doetschman T. 2009. Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development. Dev Dyn 238(2):431-42. [PubMed: 19161227] [MGI Ref ID J:144180]
Cui XM; Shiomi N; Chen J; Saito T; Yamamoto T; Ito Y; Bringas P; Chai Y; Shuler CF. 2005. Overexpression of Smad2 in Tgf-beta3-null mutant mice rescues cleft palate. Dev Biol 278(1):193-202. [PubMed: 15649471] [MGI Ref ID J:96461]
Dunker N; Krieglstein K. 2003. Reduced programmed cell death in the retina and defects in lens and cornea of Tgfbeta2(-/-) Tgfbeta3(-/-) double-deficient mice. Cell Tissue Res 313(1):1-10. [PubMed: 12838410] [MGI Ref ID J:105113]
Dunker N; Schmitt K; Krieglstein K. 2002. TGF-beta is required for programmed cell death in interdigital webs of the developing mouse limb. Mech Dev 113(2):111-20. [PubMed: 11960699] [MGI Ref ID J:76541]
Dunker N; Schmitt K; Schuster N; Krieglstein K. 2002. The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa. Gastroenterology 122(5):1364-75. [PubMed: 11984523] [MGI Ref ID J:76342]
Foitzik K; Paus R; Doetschman T; Dotto GP. 1999. The TGF-beta2 isoform is both a required and sufficient inducer of murine hair follicle morphogenesis. Dev Biol 212(2):278-89. [PubMed: 10433821] [MGI Ref ID J:56937]
Galloway JL; Jones SJ; Mossey PA; Ellis IR. 2013. The control and importance of hyaluronan synthase expression in palatogenesis. Front Physiol 4:10. [PubMed: 23382716] [MGI Ref ID J:195152]
Letterio JJ; Bottinger EP. 1998. TGF-beta knockout and dominant-negative receptor transgenic mice. Miner Electrolyte Metab 24(2-3):161-7. [PubMed: 9525700] [MGI Ref ID J:46776]
Li J; Foitzik K; Calautti E; Baden H; Doetschman T; Dotto GP. 1999. TGF-beta3, but not TGF-beta1, protects keratinocytes against 12-O-tetradecanoylphorbol-13-acetate-induced cell death in vitro and in vivo. J Biol Chem 274(7):4213-9. [PubMed: 9933619] [MGI Ref ID J:115227]
Martinez-Alvarez C; Blanco MJ; Perez R; Rabadan MA; Aparicio M; Resel E; Martinez T; Nieto MA. 2004. Snail family members and cell survival in physiological and pathological cleft palates. Dev Biol 265(1):207-18. [PubMed: 14697364] [MGI Ref ID J:87413]
Martinez-Sanz E; Del Rio A; Barrio C; Murillo J; Maldonado E; Garcillan B; Amoros M; Fuerte T; Fernandez A; Trinidad E; Rabadan MA; Lopez Y; Martinez ML; Martinez-Alvarez C. 2008. Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains. Differentiation 76(4):417-30. [PubMed: 18431835] [MGI Ref ID J:133954]
Mecha M; Rabadan MA; Pena-Melian A; Valencia M; Mondejar T; Blanco MJ. 2008. Expression of TGF-betas in the embryonic nervous system: analysis of interbalance between isoforms. Dev Dyn 237(6):1709-17. [PubMed: 18498095] [MGI Ref ID J:136358]
Memon MA; Anway MD; Covert TR; Uzumcu M; Skinner MK. 2008. Transforming growth factor beta (TGFbeta1, TGFbeta2 and TGFbeta3) null-mutant phenotypes in embryonic gonadal development. Mol Cell Endocrinol 294(1-2):70-80. [PubMed: 18790002] [MGI Ref ID J:145458]
Mu Z; Yang Z; Yu D; Zhao Z; Munger JS. 2008. TGFbeta1 and TGFbeta3 are partially redundant effectors in brain vascular morphogenesis. Mech Dev 125(5-6):508-16. [PubMed: 18343643] [MGI Ref ID J:136106]
Pangas SA. 2012. Regulation of the ovarian reserve by members of the transforming growth factor beta family. Mol Reprod Dev 79(10):666-79. [PubMed: 22847922] [MGI Ref ID J:190579]
Pryce BA; Watson SS; Murchison ND; Staverosky JA; Dunker N; Schweitzer R. 2009. Recruitment and maintenance of tendon progenitors by TGF{beta} signaling are essential for tendon formation. Development 136(8):1351-61. [PubMed: 19304887] [MGI Ref ID J:147280]
Roussa E; Wiehle M; Dunker N; Becker-Katins S; Oehlke O; Krieglstein K. 2006. Transforming growth factor beta is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo: ectopic induction in dorsal mesencephalon. Stem Cells 24(9):2120-9. [PubMed: 16741229] [MGI Ref ID J:174490]
Saika S; Saika S; Liu CY; Azhar M; Sanford LP; Doetschman T; Gendron RL; Kao CW; Kao WW. 2001. TGFbeta2 in corneal morphogenesis during mouse embryonic development. Dev Biol 240(2):419-32. [PubMed: 11784073] [MGI Ref ID J:73681]
Sasaki Y; O'kane S; Dixon J; Dixon MJ; Ferguson MW. 2007. Temporal and spatial expression of Pax9 and Sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos. Arch Oral Biol 52(3):260-7. [PubMed: 17097601] [MGI Ref ID J:117758]
Taya Y; O'Kane S; Ferguson MW. 1999. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development 126(17):3869-79. [PubMed: 10433915] [MGI Ref ID J:56561]
Tesseur I; Wyss-Coray T. 2006. A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered models. Curr Alzheimer Res 3(5):505-13. [PubMed: 17168649] [MGI Ref ID J:125213]
Tudela C; Formoso MA; Martinez T; Perez R; Aparicio M; Maestro C; Del Rio A; Martinez E; Ferguson M; Martinez-Alvarez C. 2002. TGF-beta3 is required for the adhesion and intercalation of medial edge epithelial cells during palate fusion. Int J Dev Biol 46(3):333-6. [PubMed: 12068957] [MGI Ref ID J:80255]
Vogel T; Ahrens S; Buttner N; Krieglstein K. 2010. Transforming growth factor beta promotes neuronal cell fate of mouse cortical and hippocampal progenitors in vitro and in vivo: identification of Nedd9 as an essential signaling component. Cereb Cortex 20(3):661-71. [PubMed: 19587023] [MGI Ref ID J:174166]
Xu X; Han J; Ito Y; Bringas P Jr; Deng C; Chai Y. 2008. Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate development. Dev Cell 15(2):322-9. [PubMed: 18694570] [MGI Ref ID J:140401]
Zhang J; Pho V; Bonasera SJ; Holtzman J; Tang AT; Hellmuth J; Tang S; Janak PH; Tecott LH; Huang EJ. 2007. Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci 10(1):77-86. [PubMed: 17159989] [MGI Ref ID J:117465]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- 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 |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- 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).
|
|
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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