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Description
Strain Information
Former Names STOCK Gt(ROSA)26Sortm1(Smo/YFP)Amc/J (Changed: 23-MAY-06 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation N?+1F9 (31-DEC-07) Donating Investigator Andrew McMahon, Harvard University Description
These mice contain an Enhanced Yellow Fluorescent Protein/Smoothened homolog (Drosophila) fusion gene inserted into the Gt(ROSA)26Sor locus. The mutant allele consists of a fusion product involving Enhanced Yellow Fluorescent Protein (EYFP) and the constitutively active W539L point mutation of the mouse smoothened homolog (Drosophila) gene (SmoM2). Expression of the Smo/EYFP fusion gene is blocked by a loxP-flanked STOP fragment placed between the Gt(ROSA)26Sor promoter and the Smo/EYFP sequence. When used in conjunction with a Cre recombinase-expressing strain, successful Cre-mediated excision results in the constitutive expression of mouse smoothened homolog (Drosophila) and unrestrained Hedgehog signaling in Cre-expressing tissues. Expression of the SmoM2 fusion protein can be monitored using EYFP-specific fluorescence protocols. Mice that are homozygous for the mutant allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.For example, when crossed to a strain expressing tamoxifen inducible Cre recombinase in developing embryos (see Stock No. 004453), in neural progenitor cells (see Stock No. 007684), in cells that received positive hedgehog signalling (see Stock No. 007913), or in cells that express Shh (see Stock No. 005623), this mutant mouse strain may be useful in studies of tumorigenic potential in the hedgehog pathway.
When bred to a strain expressing Cre recombinase in the central nervous system(see Stock No. 004600 for example), this mutant mouse strain may be useful in studies of progenitor cell involvement in the development of medulloblastomas.
When bred to a strain expressing Cre recombinase in midbrain/dorsal spinal cord (see Stock No. 007807 for example), this mutant mouse strain may be useful in studies of craniofacial development.
When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of thalamic development.
Development
A targeting vector containing a loxP flanked PGK-neo-stop cassette upstream of the Yellow Fluorescent Protein/Smoothened homolog (Drosophila) fusion gene (Smo/YFP) was inserted into the Gt(ROSA)26Sor locus. The construct was introduced into 129X1/SvJ-derived AV3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were bred to C57BL/6 and outbred Swiss Webster mice. (Additional information from Donating Investigator is forthcoming)
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
004288 129X1-Smotm1Amc/J 008831 C57BL/6-Tg(Neurod2-Smo*A1)199Jols/J 004526 STOCK Smotm2Amc/J
005483 129-Tg(CAG-EYFP)7AC5Nagy/J 006148 B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J 008299 B6.Cg-Tg(NEFL-EYFP/Nefh)40Gsn/J 007901 B6.Cg-Tg(Thy1-Brainbow1.0)HLich/J 007911 B6.Cg-Tg(Thy1-Brainbow1.1)MLich/J 007921 B6.Cg-Tg(Thy1-Brainbow2.1)RLich/J 007612 B6.Cg-Tg(Thy1-COP4/EYFP)18Gfng/J 007615 B6.Cg-Tg(Thy1-COP4/EYFP)9Gfng/J 005630 B6.Cg-Tg(Thy1-EYFP)15Jrs/J 003709 B6.Cg-Tg(Thy1-YFP)16Jrs/J 005627 B6.Cg-Tg(Thy1-YFP/Syp)10Jrs/J 003782 B6.Cg-Tg(Thy1-YFPH)2Jrs/J 007606 B6.Cg-Tg(Thy1-cre/ESR1,-EYFP)AGfng/J 008636 B6;C-Tg(Prnp-APP695*/EYFP)49Gsn/J 007910 B6;CBA-Tg(Thy1-Brainbow1.0)LLich/J 005620 B6;D2-Tg(S100B-EYFP)1Wjt/J 007610 B6;SJL-Tg(Thy1-cre/ESR1,-EYFP)VGfng/J 007880 B6SJL-Tg(Thy1-Stx1a/EYFP)1Sud/J 006618 C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J 006362 C57BL/6J-Tg(CMV-Cox8a/EYFP)17J/J 007857 C57BL/6J-Tg(Eno2-YFP/Cox8a)YRwb/J 007860 C57BL/6J-Tg(Eno2-YFP/Cox8a)ZRwb/J 009422 NOD.Cg-Tg(Itgax-EYFP)1Mnz/QtngJ
Additional Web Information
Fluorescent Proteins/lacZ Systems
Introduction to Cre-lox technology
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/?
involves: 129X1/SvJ
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:114992)
- no tumors are observed up to 12 months of age
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Gli1tm3(cre/ESR1)Alj/Gli1+ Gt(ROSA)26Sortm1(Smo/EYFP)Amc/Gt(ROSA)26Sortm1(Smo/EYFP)Amc
involves: 129S6/SvEvTac * 129X1/SvJ (conditional)
- life span-post-weaning/aging
- premature death (MGI Ref ID J:139574)
- mice survive 45 days
- tumorigenesis
- medulloblastoma (MGI Ref ID J:139574)
- all mice develop medulloblastomas that are located in lobes VI through IX and have a mean survival of 45 days
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/Gt(ROSA)26Sor+ Tg(Nes-cre)1Kln/0
involves: 129X1/SvJ * C57BL/6 * SJL (conditional)
- lethality-prenatal/perinatal
- neonatal lethality (MGI Ref ID J:147427)
- animals die by the end of the first postnatal day (P0)
- nervous system phenotype
- abnormal thalamus morphology (MGI Ref ID J:147427)
- based on cell fate analysis and molecular marker analysis, the intergeniculate leaflet (IGL) nucleus is expanded caudodorsally along the surface of the diencephalon at E16.5
- abnormal lateral geniculate nucleus morphology (MGI Ref ID J:147427)
- based on cell fate analysis and molecular marker analysis, the dorsal lateral geniculate (dLG) nucleus is expanded caudodorsally along the surface of the diencephalon at E16.5
- increased brain size (MGI Ref ID J:147427)
- in all embryos, brain size is larger than in controls, especially in the dorsal telencephalon
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/Gt(ROSA)26Sortm1(Smo/EYFP)Amc Shhtm2(cre/ESR1)Cjt/Shh+
involves: 129X1/SvJ (conditional)
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:139574)
- following induction with tamoxifen, mice do not exhibit medulloblastoma
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/Gt(ROSA)26Sortm1(Smo/EYFP)Amc Tg(Atoh1-cre/ESR1)14Fsh/0
involves: 129X1/SvJ * FVB/N (conditional)
- life span-post-weaning/aging
- premature death (MGI Ref ID J:139574)
- mice survive 41 days
- nervous system phenotype
- abnormal external granule cell layer morphology (MGI Ref ID J:139574)
- mice exhibit hyperplasia on the external granule cell layer beginning at P0 and more prominently at P7
- tumorigenesis
- medulloblastoma (MGI Ref ID J:139574)
- all mice develop diffuse medulloblastomas and have a mean survival of 41 days
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/Gt(ROSA)26Sortm1(Smo/EYFP)Amc Tg(GFAP-cre)25Mes/0
involves: 129X1/SvJ * FVB/N (conditional)
- life span-post-weaning/aging
- premature death (MGI Ref ID J:139574)
- mice survive 57 days
- tumorigenesis
- medulloblastoma (MGI Ref ID J:139574)
- mice develop diffuse medulloblastoma tumors and have a mean survival of 57 days
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/? Tg(CAG-cre/Esr1)5Amc/?
involves: 129X1/SvJ * C57BL/6 * CBA (conditional)
- life span-post-weaning/aging
- premature death (MGI Ref ID J:114992)
- following tamoxifen treatment, all mice are dead by 18 weeks of observation unlike untreated mice and Ptch1tm1Mps heterozygotes
- tumorigenesis
- basal cell carcinoma (MGI Ref ID J:114992)
- following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks
- medulloblastoma (MGI Ref ID J:114992)
- found in 27% of mice and 40% of mice following tamoxifen treatment
- rhabdomyosarcoma (MGI Ref ID J:114992)
- present without tamoxifen treatment (average number 3)
- following tamoxifen treatment, the multiplicity of tumors is increased (average number 7)
- mostly confined to rear thigh and abdominal wall
- following tamoxifen treatment, tumors are detected in skeletal muscle of the head, neck, tongue and paratesticular regions
- following tamoxifen treatment at P10, age of onset is accelerated to week 5 compared to week 9 in untreated mice
- digestive/alimentary phenotype
- abnormal pancreas morphology (MGI Ref ID J:114992)
- cystic metaplastic lesions are observed with increased frequency following tamoxifen treatment
- gastric polyps (MGI Ref ID J:114992)
- diverticular harmatomatous lesions in the stomach occur at a higher rate following treatment with tamoxifen (less than 5% of mice after treatment)
- intestinal polyps (MGI Ref ID J:114992)
- diverticular harmatomatous lesions in the intestine occur at a higher rate following treatment with tamoxifen (20% without treatment and 80% following treatment)
- endocrine/exocrine gland phenotype
- abnormal pancreas morphology (MGI Ref ID J:114992)
- cystic metaplastic lesions are observed with increased frequency following tamoxifen treatment
- skin/coat/nails phenotype
- basal cell carcinoma (MGI Ref ID J:114992)
- following tamoxifen treatment, mice exhibit macroscopic basal cell carcinomas (BBC) where as all other mice develop BBC tumors at 8 weeks
Gt(ROSA)26Sortm1(Smo/EYFP)Amc/? Tg(Wnt1-cre)11Rth/?
involves: 129X1/SvJ * C57BL/6J * CBA/J (conditional)
- craniofacial phenotype
- abnormal craniofacial development (MGI Ref ID J:89445)
- at E10.5, facial processes are mildly hyperplastic
- at E12.5, gross organization of the face is disrupted
- most of the head skeleton fails to form
This mouse can be used to support research in many areas including:
Smo relatedNeurobiology Research
Cre-lox System
loxP-flanked Sequences: Test/Reporter
Research Tools
Cre-lox System
loxP-flanked Sequences: Test/Reporter
Developmental Biology Research
Cre-lox System
Fluorescent Proteins
Gt(ROSA)26Sortm1(Smo/EYFP)Amc relatedDevelopmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
heart
Neural Tube Defects
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Gt(ROSA)26Sortm1(Smo/EYFP)Amc | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Andrew P McMahon | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Gt(ROSA)26Sortm1(smo/YFP)Amc; R26SmoM2; R26SmoM2; SmoM2-YFPfl; | ||
| Mutation Made By | Junhao Mao, Harvard University | ||
| Strain of Origin | 129X1/SvJ | ||
| ES Cell Line Name | AV3 | ||
| ES Cell Line Strain | 129X1/SvJ | ||
| Site of Expression | when crossed to a Cre recombinase-expressing strain, expression of Enhanced Yellow Fluorescent Protein and the mouse smoothened homolog (Drosophila) protein is observed in the cre-expressing tissues, leading to unrestrained Hedgehog signaling | ||
| Expressed Gene | YFP, Yellow Fluorescent Protein, jellyfish | ||
| Yellow Fluorescent Protein (YFP) is a derivative of Green Fluorescent Protein (GFP), a versatile reporter molecule which has found use in many biological applications. The original molecule has been modified in order to enhance fluorescence intensity and shift the wavelength emitted when excited. When YFP is utilized in a transgenic construct, tissue expressing sufficient amounts of YFP will fluoresce yellowish-green when exposed to a 513 nm light source. | |||
| Expressed Gene | Smo, smoothened homolog (Drosophila), mouse, laboratory | ||
| Molecular Note | A loxP flanked PGK-neo-stop cassette upstream of the Yellow Fluorescent Protein/Smoothened homolog (Drosophila) fusion gene (Smo/EYFP) was inserted into the Gt(ROSA)26Sor locus. The mutant allele consists of a fusion product involving Yellow FluorescentProtein and the constitutively active W539L point mutation of the mouse smoothened homolog (Drosophila) gene (SmoM2). Expression of the Smo/EYFP fusion gene is blocked by a loxP-flanked STOP fragment placed between the Gt(ROSA)26Sor promoter and the Smo/EYFP sequence. [MGI Ref ID J:89445] | ||
| Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | AV258896; Gtrgeo26; Gtrosa26; R26; ROSA26; beta geo; expressed sequence AV258896; gene trap ROSA 26; gene trap ROSA b-geo 26; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Gt(ROSA)26Sortm1(Smo/EYFP)Amc, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Jeong J; Mao J; Tenzen T; Kottmann AH; McMahon AP. 2004. Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. Genes Dev 18(8):937-51. [PubMed: 15107405] [MGI Ref ID J:89445]
Additional References
Gt(ROSA)26Sortm1(Smo/EYFP)Amc relatedGao J; Graves S; Koch U; Liu S; Jankovic V; Buonamici S; El Andaloussi A; Nimer SD; Kee BL; Taichman R; Radtke F; Aifantis I. 2009. Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 4(6):548-58. [PubMed: 19497283] [MGI Ref ID J:149820]
Han YG; Kim HJ; Dlugosz AA; Ellison DW; Gilbertson RJ; Alvarez-Buylla A. 2009. Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 15(9):1062-5. [PubMed: 19701203] [MGI Ref ID J:154130]
Han YG; Spassky N; Romaguera-Ros M; Garcia-Verdugo JM; Aguilar A; Schneider-Maunoury S; Alvarez-Buylla A. 2008. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11(3):277-84. [PubMed: 18297065] [MGI Ref ID J:135664]
Heine VM; Rowitch DH. 2009. Hedgehog signaling has a protective effect in glucocorticoid-induced mouse neonatal brain injury through an 11betaHSD2-dependent mechanism. J Clin Invest 119(2):267-77. [PubMed: 19164857] [MGI Ref ID J:146149]
Huang X; Ketova T; Fleming JT; Wang H; Dey SK; Litingtung Y; Chiang C. 2009. Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus. Development 136(15):2535-43. [PubMed: 19570847] [MGI Ref ID J:152851]
Hyman JM; Firestone AJ; Heine VM; Zhao Y; Ocasio CA; Han K; Sun M; Rack PG; Sinha S; Wu JJ; Solow-Cordero DE; Jiang J; Rowitch DH; Chen JK. 2009. Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade. Proc Natl Acad Sci U S A 106(33):14132-7. [PubMed: 19666565] [MGI Ref ID J:151950]
Li Y; Gordon J; Manley NR; Litingtung Y; Chiang C. 2008. Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis. Dev Biol 322(1):145-55. [PubMed: 18692041] [MGI Ref ID J:142133]
Mao J; Ligon KL; Rakhlin EY; Thayer SP; Bronson RT; Rowitch D; McMahon AP. 2006. A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway. Cancer Res 66(20):10171-8. [PubMed: 17047082] [MGI Ref ID J:114992]
Olsen O; Funke L; Long JF; Fukata M; Kazuta T; Trinidad JC; Moore KA; Misawa H; Welling PA; Burlingame AL; Zhang M; Bredt DS. 2007. Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice. J Cell Biol 179(1):151-64. [PubMed: 17923534] [MGI Ref ID J:134806]
Ren Y; Cowan RG; Harman RM; Quirk SM. 2009. Dominant activation of the hedgehog signaling pathway in the ovary alters theca development and prevents ovulation. Mol Endocrinol 23(5):711-23. [PubMed: 19196835] [MGI Ref ID J:147787]
Schuller U; Heine VM; Mao J; Kho AT; Dillon AK; Han YG; Huillard E; Sun T; Ligon AH; Qian Y; Ma Q; Alvarez-Buylla A; McMahon AP; Rowitch DH; Ligon KL. 2008. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14(2):123-34. [PubMed: 18691547] [MGI Ref ID J:139574]
Vue TY; Bluske K; Alishahi A; Yang LL; Koyano-Nakagawa N; Novitch B; Nakagawa Y. 2009. Sonic hedgehog signaling controls thalamic progenitor identity and nuclei specification in mice. J Neurosci 29(14):4484-97. [PubMed: 19357274] [MGI Ref ID J:147427]
Wong SY; Seol AD; So PL; Ermilov AN; Bichakjian CK; Epstein EH Jr; Dlugosz AA; Reiter JF. 2009. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 15(9):1055-61. [PubMed: 19701205] [MGI Ref ID J:154128]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $171.20 Female or Male Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc
Pairs /Price (US dollars $) Pair Genotype $342.40 Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc x Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $222.60 Female or Male Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc
Pairs /Price (US dollars $) Pair Genotype $445.20 Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc x Homozygous for Gt(ROSA)26Sortm1(Smo/EYFP)Amc
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| None Available | ||
| 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 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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