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| 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. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
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- Health & husbandry
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Description
Strain Information
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System +/+ sibling x Heterozygote (Female x Male) 03-FEB-09 Species laboratory mouse Generation N8+ (02-FEB-09) Donating Investigator Andrew McMahon, Harvard University 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 bred with C57BL/6 mice for approximately 7 generations prior to arrival at The Jackson Laboratory. Upon arrival, these mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
004293 129-Shhtm2Amc/J 000214 B10.D2/nSn-ShhHx/J 005623 B6.129S-Shhtm2(cre/ESR1)Cjt/J 005622 B6.Cg-Shhtm1(EGFP/cre)Cjt/J 003318 STOCK Shhtm1Amc/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Shhtm6Amc/Shhtm6Amc
Background Not Specified
- lethality-prenatal/perinatal
- lethality throughout fetal growth and development (MGI Ref ID J:132152)
- 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
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
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Shhtm6Amc | ||
|---|---|---|---|
| Allele Name | targeted mutation 6, Andre P McMahon | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Shh::GFP; | ||
| Mutation Made By | Andrew McMahon, Harvard University | ||
| Site of Expression | early neuronal precursors | ||
| Gene Symbol and Name | Shh, sonic hedgehog | ||
| Chromosome | 5 | ||
| Gene Common Name(s) | Dsh; HHG1; HLP3; HPE3; Hhg1; Hx; Hxl3; M100081; MCOPCB5; SMMCI; TPT; TPTPS; hedgehog gene 1; hemimelic extra toes; hemimelic extratoes like 3; short digits; | ||
| 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. Thisallele produces functional albeit inefficient protein product. [MGI Ref ID J:132152] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Shhtm6Amc, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
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 Ref ID J:132152]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together, to wildtype littermates, or to C57BL/6J inbred mice. Homozygotes are stillborn with developmental defects. Mating System +/+ sibling x Heterozygote (Female x Male) 03-FEB-09 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 11-JAN-10
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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. | ||
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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.Ordering and Purchasing Information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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