Overview

Also Known As:Tulp3-

These Tulp3 knock-out mice exhibit failure of neural tube closure, and die by embryonic day 14.5. They are suitable for use in applications related to studies of sonic hedgehog (Shh) mediated signaling in embryonic development.

Genetic overview

Genetic Background	Generation

Tulp3^tm1Jng

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Tulp3	tubby-like protein 3

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Research Applications

Developmental Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The tubby-like protein 3 (Tulp3) gene has been identified as a member of a small novel gene family that is primarily neuronally expressed, and is involved in the sonic hedgehog (Shh) and modulation of the Shh signaling pathway. Embryos homozygous for the Tulp3^tm1Jng mutant allele exhibit failure of neural tube closure, and die by embryonic day 14.5. Failure of cranial neural tube closure coincided with increased neuroepithelial apoptosis specifically in the hindbrain and the caudal neural tube. In addition, the number of betaIII-tubulin positive cells is significantly decreased in the hindbrain of Tulp3^tm1Jng(-/-) embryos. Some Tulp3^tm1Jng heterozygotes also manifest embryonic lethality with neuroepithelial cell death.

Development

The targeting construct (described elsewhere) was electroporated into 129-derived R1 embryonic stem cells. Chimeric mice were crossed to 129S1/SvImJ and maintained by intercross. Embryos were cryopreserved using 129X1/SvJ oocyte donors.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Embryo

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Ikeda A; Ikeda S; Gridley T; Nishina PM; Naggert JK. 2001. Neural tube defects and neuroepithelial cell death in Tulp3 knockout mice. Hum Mol Genet 10(12):1325-34PubMed: 11406614 MGI: J:70060

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Genetics

Tulp3^tm1Jng

Allele Symbol: Tulp3^tm1Jng

Allele Name	targeted mutation 1, Jurgen Naggert
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Tulp3^-
Gene Symbol and Name	Tulp3, tubby-like protein 3
Gene Synonym(s)
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Embryo
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	6
Molecular Note	A portion of exon 5 and exons 6-9 were removed and replaced with an in-frame GFP-neo construct via homologous recombination. The targeted mutation results in deletion of the C-terminus and part of the N-terminal region of the protein, and creates a fusion protein with GFP. Homozygous mutant embryos were identified by PCR genotype analysis.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Tulp3^tm1Jng related

Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Neural Tube Defects
Neurobiology Research
- Neural Tube Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Tulp3^tm1Jng/Tulp3^tm1Jng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system phenotype

internal hemorrhage
- at E10.5 to E13.5, homozygous mutant embryos display hemorrhagic sites in the brain and along the caudal neural tube
- Normal - however, vascular formation remains unaffected at E10.5

intracranial hemorrhage
- at E10.5, homozygous mutant embryos show hemorrhage into the telencephalic vesicles

growth/size/body region phenotype

facial cleft
- at E12.5, mutant nasal prominencesare not completely merged with each other and to the maxillary prominences

hematopoietic system phenotype

anemia
- at E14.5, all homozygous mutant embryos lack circulating red blood cells

integument phenotype

pallor
- at E14.5, all homozygous mutant embryos are pale

mortality/aging

lethality throughout fetal growth and development, complete penetrance
- homozygous mutant embryos die by E14.5

nervous system phenotype

abnormal dorsal root ganglion morphology
- at E12.5 and E13.5, mutant dorsal root ganglia are irregular in size and shape, and are sometimes not segmented
- Normal - however, no obvious somite patterning defect is detected

abnormal hindbrain development
- at E9.5, the mutant hindbrain fails to elevate and forms a convex configuration instead of the V-shaped neural tube observed in wild-type embryos

abnormal hindbrain morphology
- at E9.5, the hindbrain neuroepithelium is not fused and the hindbrain appears morphologically abnormal

abnormal midbrain morphology
- at E9.5, the rostral midbrain appears morphologically abnormal

abnormal neural tube morphology
- at E10.5, ~63% of homozygous mutant embryos show NTDs
- starting at E9.5, homozygotes display neural tube defects (NTDs), with both the anterior midbrain and the hindbrain being open

abnormal neuron specification
- at E9.5 and E10.5, the number of betaIII-tubulin positive cells is significantly reduced in the hindbrain of mutant embryos

exencephaly
- at E12.5, 77% of homozygous mutant embryos display exencephaly resulting from NTDs, while the remaining embryos dot not exhibit NTDs

increased embryonic neuroepithelium apoptosis
- at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain, as shown by TUNEL assays

intracranial hemorrhage
- at E10.5, homozygous mutant embryos show hemorrhage into the telencephalic vesicles

open neural tube
- at E9.5, homozygous mutant embryos display an open and everted neural tube

spina bifida
- at E12.5 and E13.5, 37% of homozygous mutant embryos display spina bifida in the posterior neuropore (caudal zone)

skeleton phenotype

abnormal vertebrae morphology
- at E12.5 and E13.5, mutant vertebrae display a disorganized structure

cellular phenotype

increased apoptosis
- at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain and in the caudal neural tube, as shown by TUNEL assays

increased embryonic neuroepithelium apoptosis
- at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain, as shown by TUNEL assays

craniofacial phenotype

abnormal craniofacial development
- at E11.5-E12.5, all homozygous mutant embryos show abnormal craniofacial development, partly due to increased cell death in the neuroepithelium of the hindbrain

facial cleft
- at E12.5, mutant nasal prominencesare not completely merged with each other and to the maxillary prominences

embryo phenotype

abnormal neural tube morphology
- at E10.5, ~63% of homozygous mutant embryos show NTDs
- starting at E9.5, homozygotes display neural tube defects (NTDs), with both the anterior midbrain and the hindbrain being open

open neural tube
- at E9.5, homozygous mutant embryos display an open and everted neural tube

spina bifida
- at E12.5 and E13.5, 37% of homozygous mutant embryos display spina bifida in the posterior neuropore (caudal zone)

Genotype: Tulp3^tm1Jng/Tulp3⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system phenotype

hemorrhage
- some heterozygous mutant embryos display sites of hemorrhage at E12.5 and blood loss at E14.5

cellular phenotype

increased embryonic neuroepithelium apoptosis
- at E10.5, affected heterozygous mutant embryos display excessive apoptosis of neuroepithelial cells in the hindbrain region

embryo phenotype

open neural tube
- at E10.5, a few heterozygotes exhibit an open neural tube

mortality/aging

embryonic lethality, incomplete penetrance
- affected heterozygous mutant embryos exhibit embryonic lethality with excessive neuroepithelial apoptosis in the hindbrain
- Normal - however, no overt abnormalities are detected in live-born heterozygous mutant mice

nervous system phenotype

abnormal brain development
- at E10.5, the majority of affected heterozygous mutant embryos display abnormal fore-, mid- and hindbrain development

abnormal brain morphology
- at E10.5, 18% of heterozygous mutant embryos display an abnormal brain phenotype that is less severe than that observed in homozygous mutant embryos

abnormal forebrain morphology
- at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized forebrain

abnormal hindbrain morphology
- at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized hindbrain with a collapsed roof

abnormal midbrain morphology
- at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized midbrain

forebrain hypoplasia

increased embryonic neuroepithelium apoptosis
- at E10.5, affected heterozygous mutant embryos display excessive apoptosis of neuroepithelial cells in the hindbrain region

open neural tube
- at E10.5, a few heterozygotes exhibit an open neural tube

References

Ikeda A; Ikeda S; Gridley T; Nishina PM; Naggert JK. 2001. Neural tube defects and neuroepithelial cell death in Tulp3 knockout mice. Hum Mol Genet 10(12):1325-34PubMed: 11406614 MGI: J:70060

Additional - Tulp3^tm1Jng related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tulp3
- Genotyping resources and troubleshooting
Citation
When using the Tulp3- mouse strain in a publication, please cite the originating article(s) and include JAX stock #005291 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/Product	Description	Price
	Heterozygous or Wild-type for Tulp3<tm1Jng>

Related Products and Services

Frozen Mouse Embryo	129-Tulp3<tm1Jng>/Pjn Frozen Embryos	$2595.00
Frozen Mouse Embryo	129-Tulp3<tm1Jng>/Pjn Frozen Embryos	$2595.00
Frozen Mouse Embryo	129-Tulp3<tm1Jng>/Pjn Frozen Embryos	$3373.50
Frozen Mouse Embryo	129-Tulp3<tm1Jng>/Pjn Frozen Embryos	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:Tulp3-

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tulp3tm1Jng

Allele Symbol: Tulp3tm1Jng

Disease Terms

Research Areas By Phenotype

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

Genotype: Tulp3tm1Jng related

Mammalian Phenotype Terms by Genotype

Genotype: Tulp3tm1Jng/Tulp3tm1Jnginvolves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

integument phenotype

mortality/aging

nervous system phenotype

skeleton phenotype

cellular phenotype

craniofacial phenotype

embryo phenotype

Genotype: Tulp3tm1Jng/Tulp3+involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system phenotype

cellular phenotype

embryo phenotype

mortality/aging

nervous system phenotype

References

Additional - Tulp3tm1Jng related

Genotyping Protocols

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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tulp3^tm1Jng

Allele Symbol: Tulp3^tm1Jng

Genotype: Tulp3^tm1Jng related

Genotype: Tulp3^tm1Jng/Tulp3^tm1Jng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Genotype: Tulp3^tm1Jng/Tulp3⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Additional - Tulp3^tm1Jng related