Overview

The Tgfb3 gene is replaced with a Tgfb1 cDNA in these mice, abolishing Tgfb3 expression. TGFB1 expression partially rescues the clefting phenotype associated with Tgfb3 disruption. These mice may be suitable for use in studies examining the isoform-specific roles of transforming growth factors.

Donating Investigator

Dr. Vesa Kaartinen, University of Michigan

Genetic overview

Genetic Background	Generation

Tgfb3^tm2(Tgfb1)Vk

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout, Inserted expressed sequence)	Tgfb3	transforming growth factor, beta 3

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Research Applications

Developmental Biology Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

In this knock in/out mutant, the transforming growth factor, beta 3 (Tgfb3) coding region was replaced with a transforming growth factor, beta 1 (Tgfb1) cDNA, abolishing Tgfb3 expression. TGFB isoforms are important regulators of cell growth, cell differentiation, apoptosis, and cellular homeostasis. TGFB3 is expressed in the prefusion palatal epithelium and KO models display a cleft of the secondary palate, lung hypoplasia, respiratory distress, hemothorax, and neonatal lethality. When TGFB1 is knocked into the TGFB3 coding region, the clefting phenotype is partially rescued. These mutant mice show partial fusion of the secondary palate. They exhibit a reduction in apoptosis in the midline epithelium during fusion of the palatal shelves, causing anterior and posterior regions of the palate to not fuse. Homozygous mice are viable but do not survive past 2 weeks of age due to failure to feed.

Development

A targeting vector was designed to insert transforming growth factor, beta 1 (Tgfb1) cDNA, followed by a polyadenylation sequence and a loxP-flanked neomycin resistance cassette, into the transforming growth factor, beta 3 (Tgfb3) coding region. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to B6xCBA F1 females to generate a colony of Tgfb1-KI mice. These mice were maintained on a mixed genetic background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Expression Data

Expressed Gene	Tgfb1, transforming growth factor, beta 1, mouse, laboratory
Site of Expression

Selected References

Yang LT; Kaartinen V. 2007. Tgfb1 expressed in the Tgfb3 locus partially rescues the cleft palate phenotype of Tgfb3 null mutants. Dev Biol 312(1):384-95PubMed: 17967447 MGI: J:128938

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Genetics

Tgfb3^tm2(Tgfb1)Vk

Allele Symbol: Tgfb3^tm2(Tgfb1)Vk

Allele Name	targeted mutation 2, Vesa Kaartinen
Allele Type	Targeted (Null/Knockout, Inserted expressed sequence)
Allele Synonym(s)	Tgfb3^tm2(Tgfb1)Vk; targeted mutation 2, Vesa Kaartinen
Gene Symbol and Name	Tgfb3, transforming growth factor, beta 3
Gene Synonym(s)	RNHF; ARVD; TGF-B3; TGF-beta3; Tgfb-3; ARVD1; Tgfb-3; LDS5
Expressed Gene	Tgfb1, transforming growth factor, beta 1, mouse, laboratory
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	12
Molecular Note	A vector containing Tgfb1 cDNA followed by a pgk polyA sequence and a loxP flanked neomycin resistance cassette was inserted into the ATG start site of the targeted gene. Quantitative RT-PCR of RNA isolated from the tips of the palatal shelves demonstrates high Tgfb1 expression but no Tgfb3 expression in homozygotes.
Mutations Made By	Dr. Vesa Kaartinen, University of Michigan

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Craniofacial and Palate Defects
  - cleft palate and cleft lip

Mammalian Phenotype Terms by Genotype

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

Genotype: Tgfb3^tm2(Tgfb1)Vk/Tgfb3^tm2(Tgfb1)Vk
involves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

abnormal suckling behavior
- pups fail to suckle

mortality/aging

postnatal lethality, complete penetrance
- pups do not survive past two weeks of age

respiratory system phenotype

abnormal nasal septum morphology
- the nasal septum fails to fuse with the anterior palate in E17 embryos

craniofacial phenotype

abnormal nasal septum morphology
- the nasal septum fails to fuse with the anterior palate in E17 embryos

abnormal palatal shelf fusion at midline
- reduced apoptosis occurs in the midline epithelium during fusion
- shelves do not fuse at the most anterior and posterior regions of the palate

cleft palate
- clefts occur at the junction of the primary and secondary palates and in the posterior region of E17 embryos

digestive/alimentary phenotype

abnormal palatal shelf fusion at midline
- reduced apoptosis occurs in the midline epithelium during fusion
- shelves do not fuse at the most anterior and posterior regions of the palate

cleft palate
- clefts occur at the junction of the primary and secondary palates and in the posterior region of E17 embryos

growth/size/body region phenotype

abnormal nasal septum morphology
- the nasal septum fails to fuse with the anterior palate in E17 embryos

abnormal palatal shelf fusion at midline
- reduced apoptosis occurs in the midline epithelium during fusion
- shelves do not fuse at the most anterior and posterior regions of the palate

cleft palate
- clefts occur at the junction of the primary and secondary palates and in the posterior region of E17 embryos

References

Yang LT; Kaartinen V. 2007. Tgfb1 expressed in the Tgfb3 locus partially rescues the cleft palate phenotype of Tgfb3 null mutants. Dev Biol 312(1):384-95PubMed: 17967447 MGI: J:128938

Additional - Tgfb3^tm2(Tgfb1)Vk related

Technical Support

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Genotyping Protocols
- Separated PCR: Tgfb3^tm2(Tgfb1)Vk
- Separated MCA: Tgfb3^tm2(Tgfb1)Vk
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together or to wildtype mice from the colony. The donating investigator reports that homozygous mice are viable but do not survive past 2 weeks of age due to failure to feed.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Tgfb3^tm2(Tgfb1)Vk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018624 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Tgfb3<tm2(Tgfb1)Vk>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Selected References

Tgfb3tm2(Tgfb1)Vk

Allele Symbol: Tgfb3tm2(Tgfb1)Vk

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tgfb3tm2(Tgfb1)Vk/Tgfb3tm2(Tgfb1)Vkinvolves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

mortality/aging

respiratory system phenotype

craniofacial phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

References

Additional - Tgfb3tm2(Tgfb1)Vk related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tgfb3^tm2(Tgfb1)Vk

Allele Symbol: Tgfb3^tm2(Tgfb1)Vk

Genotype: Tgfb3^tm2(Tgfb1)Vk/Tgfb3^tm2(Tgfb1)Vk
involves: 129S1/Sv * 129X1/SvJ

Additional - Tgfb3^tm2(Tgfb1)Vk related