JAX Mouse Strain Datasheet - 008466

B6.129X1(Cg)-Shh^tm6Amc/J

Stock No:: 008466

Targeted Mutation

Cryo Recovery

Overview

These Shh::gfp mice harbor a targeted mutation of the Sonic hedgehog (Shh) locus that secretes, after normal Shh processing, a bioactive GFP-tagged Shh signaling ligand (N-Shh::GFPp). These Shh::gfp may be useful to directly visualize the function of Shh ligand in an in vivo context, such as during neural tube patterning.

Donating Investigator

Andrew P McMahon, University of Southern California

Genetic overview

Genetic Background	Generation

Shh^tm6Amc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout, Reporter)	Shh	sonic hedgehog

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Research Applications

Developmental Biology Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

While mice heterozygous for the Shh::gfp allele are viable, fertile, and indistinguishable from wild-type littermates, homozygotes are stillborn and show developmental defects consistent with reduced Sonic Hedgehog (Shh) signaling. The Shh::gfp mutation has GFP inserted into the endogenous Shh processing site (and adds a new processing site after the GFP). Thus normal Shh processing leads to secretion of the GFP-tagged Shh signaling ligand (N-Shh::GFPp) instead of wild-type Shh; with N-Shh::GFPp retaining both GFP and lipid modifications post-processing. Biochemical and cellular analysis indicates that Shh::GFP undergoes correct processing to produce active, bi-lipidated signaling peptides. Shh::GFP processing is, however, less efficient and results in reduced levels of Shh::GFP compared with wild-type Shh protein. These Shh::gfp mice produce bioactive, fluorescently labeled Shh from the endogenous Shh locus and may be useful to directly visualize the function of Shh ligand in an in vivo context, such as during neural tube patterning. In addition, these mice may also be useful in conjunction with other Sonic Hedgehog (Shh) mutant strains including Shh knockout mice (Stock No. 003318), Shh-floxed mice (Stock No. 004293), Shh-GFP/cre mice (Stock No. 005622), and Shh-creERT2 mice (Stock No. 005623).

Development

A targeting vector was designed to replace the endogenous intein cleavage-cholesterol attachment site (Shh processing site) in exon 3 of the targeted gene with a Green Fluorescent Protein (GFP) followed by a new intein cleavage-cholesterol attachment site (Shh processing site), as well as insert a frt-flanked PGK-Neo cassette in intron 2. The donating investigator reports that this construct was microinjected into 129X1/SvJ-derived AV3 embryonic stem (ES) cells, correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred to C57BL/6 inbred mice to generate Shh::gfp mice. These Shh::gfp mice were reported to have been bred with C57BL/6 mice for a small number generations prior to sending to The Jackson Laboratory Repository in 2008 (see SNP notes below). Upon arrival, these mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony. Over the next two years, the colony was backcrossed to C57BL/6J and/or wildtype mice from the colony for several additional generations. By March 2011, the colony was found to be ~96% C57BL/6 genetic background by SNP analysis (see SNP notes below).

In 2009, a 27 SNP (single nucleotide polymorphism) panel analysis performed on the rederived living colony at The Jackson Laboratory Repository. This revealed 16 markers (across several different chromosomes) that were not C57BL/6 allele-type. These data suggest the strain was sent to The Jackson Laboratory Repository with multiple sources of genetic background contamination (more than 129 genetic background).

In 2011, a 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the colony at The Jackson Laboratory Repository. This revealed one marker on chromosome 1 (~89.1 Mbp) that was not fixed for C57BL/6 allele-type (e.g.: still segregating for 129X1 allele-type).

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	early neuronal precursors

Selected References

Chamberlain CE; Jeong J; Guo C; Allen BL; McMahon AP. 2008. Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning. Development 135(6):1097-106. PubMed: 18272593 MGI: J:132152

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Genetics

Shh^tm6Amc

Allele Symbol: Shh^tm6Amc

Allele Name	targeted mutation 6, Andre P McMahon
Allele Type	Targeted (Null/Knockout, Reporter)
Allele Synonym(s)	Shh::GFP
Gene Symbol and Name	Shh, sonic hedgehog
Gene Synonym(s)	Dsh; HHG1; HLP3; HPE3; Hhg1; Hhg1; Hx; Hx; Hxl3; Hxl3; M100081; MCOPCB5; SMMCI; TPT; TPTPS; hedgehog gene 1; hemimelic extra toes; hemimelic extratoes like 3; short digits
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	early neuronal precursors
Strain of Origin	Not Specified
Chromosome	5
Molecular Note	A GFP cassette was inserted into exon 3 and an frt-flanked neo cassette was inserted between exon 2 and 3. The presence of the fusion protein and the absence of the endogenous product was confirmed by western blot analysis on E9.5 embryo extracts. This allele produces functional albeit inefficient protein product.
Mutations Made By	Andrew McMahon, University of Southern California

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Embryonic Lethality (Homozygous)
- Limb Patterning Defects
- Neural Tube Defects
- Skeletal Defects
Neurobiology Research
- Fluorescent protein expression in neural tissue
Research Tools
- Fluorescent Proteins

Genotype: GFP related

Research Tools
- Fluorescent Proteins

Mammalian Phenotype Terms by Genotype

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

Genotype: Shh^tm6Amc/Shh^tm6Amc
Not Specified

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance
- homozygous mice are still born and show defects consistent with reduced Shh signaling
- neural tube at E10.5 show all Shh-dependent neural progenitor domains resulting in normal induction of floor plate

References

Chamberlain CE; Jeong J; Guo C; Allen BL; McMahon AP. 2008. Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning. Development 135(6):1097-106. PubMed: 18272593 MGI: J:132152

Additional - Shh^tm6Amc related

Chatterjee M; Guo Q; Weber S; Scholpp S; Li JY. 2014. Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates. BMC Biol 12:13. PubMed: 24528677 MGI: J:224508

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wild-type for Shh<tm6Amc>

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 10 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.

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.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

Terms of Use

General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Selected References

Shhtm6Amc

Allele Symbol: Shhtm6Amc

Disease Terms

Research Areas By Genotype

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

Genotype: GFP related

Mammalian Phenotype Terms by Genotype

Genotype: Shhtm6Amc/Shhtm6AmcNot Specified

mortality/aging

References

Additional - Shhtm6Amc 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

Progeny testing is not required

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

Shh^tm6Amc

Allele Symbol: Shh^tm6Amc

Genotype: Shh^tm6Amc/Shh^tm6Amc
Not Specified

Additional - Shh^tm6Amc related