JAX
Mouse Strain Datasheet - 005622
B6.Cg-Shhtm1(EGFP/cre)Cjt/J
Also Known As: Shhgfpcre
Fluorescence in these mice, consistent with the endogenous Shh locus, is detected in the distal posterior region of the limb buds of embryos aged embryonic day 10 to 12. Mice homozygous for the mutation develop a limited limb skeleton and lack digit 2. This mutant mouse strain may be useful in studies of limb patterning and development.
Donating Investigator
Clifford J Tabin, Harvard Medical School
Genetic overview
| Genetic Background | Generation |
|---|---|
|
N7F10
|
Shhtm1(EGFP/cre)Cjt
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout, Recombinase-expressing) | Shh | sonic hedgehog |
Base Price
Starting at:
| $263.00 Domestic price for female |
| $337.00 Domestic price for breeder pair |
Detailed Description
This strain expresses a fusion product involving Enhanced Green Fluorescent Protein (EGFP) and Cre recombinase from the endogenous Shh locus. EGFP and cre expression are consistent with the endogenous gene. Fluorescence is detected in the distal posterior region of the limb buds of embryos aged embryonic day 10 to 12 and colocalizes with the endogenous gene product (mRNA). The donating investigator reports that it is not uncommon for a mosaic expression pattern to be exhibited when the allele is inherited through the female germline. It is recommended that this allele be passed through the male germline when conducting experiments involving cre-induced recombination. Mice homozygous for the mutation develop a limited limb skeleton and lack digit 2. Homozygous mice are not viable or fertile. Heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of limb patterning and development.
Development
A targeting vector containing a fusion product involving Enhanced Green Fluorescent Protein (EGFP) and Cre recombinase was inserted at the ATG of Shh and disrupted the sequence encoding the first 12 amino acids. The construct was electroporated into 129S6/SvEv-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and the donating investigator reported that they were then backcrossed to the same for at least 5 generations.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Expression Data
| Expressed Gene | GFP, Green Fluorescent Protein, |
|---|---|
| Expressed Gene | cre, cre recombinase, bacteriophage P1 |
| Site of Expression | Distal posterior region of the limb buds of embryos aged embryonic day 10 to 12; also a Cre strain. |
Control Suggestions
- Wild-type from the colony
- 000664 C57BL/6J
Additional Information
Selected References
- Harfe BD; Scherz PJ; Nissim S; Tian H; McMahon AP; Tabin CJ. 2004. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 118(4):517-28. PubMed: 15315763MGI: J:92504
Shhtm1(EGFP/cre)Cjt
Allele Symbol: Shhtm1(EGFP/cre)Cjt
| Allele Name | targeted mutation 1, Clifford J Tabin |
|---|---|
| Allele Type | Targeted (Null/Knockout, Recombinase-expressing) |
| Allele Synonym(s) | Shh-GFP-Cre; Shh-cre; ShhCreEGFP; ShhGFP-Cre; Shhcre/Gfp; Shhgfpcre; Shhgfp-Cre; Shhgfpcre |
| 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, |
| Expressed Gene | cre, cre recombinase, bacteriophage P1 |
| Site of Expression | Distal posterior region of the limb buds of embryos aged embryonic day 10 to 12; also a Cre strain. |
| Strain of Origin | Not Specified |
| Chromosome | 5 |
| Molecular Note | A cassette containing an in frame fusion between GFP and cre was inserted at the ATG. Upon recombination, the first 35 base pairs after the ATG were deleted. Fluorescence was detected in the distal posterior region of E10-E12 embryos. |
| Mutations Made By | Clifford Tabin, Harvard Medical School |
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
- Skeletal Defects
- Research Tools
- Cre-lox System
- Cre Recombinase Expression
- Cre Recombinase Expression: Germline/Embryonic Expression
- Developmental Biology Research
- Cre-lox System
- Fluorescent Proteins
- Genetics Research
- Mutagenesis and Transgenesis
- Mutagenesis and Transgenesis: Cre-lox System
- Cre-lox System
Genotype: GFP related
- Research Tools
- Fluorescent Proteins
Genotype: cre related
- Research Tools
- Cre-lox System
- Genetics Research
- Mutagenesis and Transgenesis
- Mutagenesis and Transgenesis: Cre-lox System
Mammalian Phenotype Terms by Genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Shhtm1(EGFP/cre)Cjt/Shhtm1(EGFP/cre)Cjt
Not Specified
cardiovascular system phenotype
- abnormal atrium myocardium morphology
- mutants show reduced muscular development in dorsal wall of atria (MGI Ref ID J:204743)
- abnormal heart left atrium morphology
- (MGI Ref ID J:204743)
- abnormal pulmonary artery morphology
- pulmonary arteries connect to aorta instead of the ouflow tract (MGI Ref ID J:204743)
- abnormal vascular smooth muscle morphology
- reduction in vascular and airway smooth muscle derived from Isl1- and Gli1-positive cardiopulmonary mesoderm progenitors is detected (MGI Ref ID J:204743)
- abnormal vasculogenesis
- embryos have a disorganized vascular endothelial plexus along anterior foregut which does not connect to heart inflow and outflow tracts (MGI Ref ID J:204743)
- absent pulmonary vein
- pulmonary veins from left atrium to lung are absent (MGI Ref ID J:204743)
muscle phenotype
- abnormal vascular smooth muscle morphology
- reduction in vascular and airway smooth muscle derived from Isl1- and Gli1-positive cardiopulmonary mesoderm progenitors is detected (MGI Ref ID J:204743)
limbs/digits/tail phenotype
- abnormal limb bone morphology
- a limited skeletal structure consisting of the humerus, radius and single digit 1 is seen (MGI Ref ID J:92504)
skeleton phenotype
- abnormal limb bone morphology
- a limited skeletal structure consisting of the humerus, radius and single digit 1 is seen (MGI Ref ID J:92504)
respiratory system phenotype
- abnormal respiratory conducting tube morphology
- airway smooth muscle derived from Isl1- and Gli1-positive cardiopulmonary mesoderm progenitors is significantly reduced; airway smooth muscle development is reduced (MGI Ref ID J:204743)
References
- Harfe BD; Scherz PJ; Nissim S; Tian H; McMahon AP; Tabin CJ. 2004. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell 118(4):517-28. PubMed: 15315763MGI: J:92504
Additional - Shhtm1(EGFP/cre)Cjt related
- Achim K; Peltopuro P; Lahti L; Li J; Salminen M; Partanen J. 2012. Distinct developmental origins and regulatory mechanisms for GABAergic neurons associated with dopaminergic nuclei in the ventral mesodiencephalic region. Development 139(13):2360-70. PubMed: 22627282MGI: J:185533
- Ahn Y; Sanderson BW; Klein OD; Krumlauf R. 2010. Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development 137(19):3221-31. PubMed: 20724449MGI: J:168361
- Anderegg A; Lin HP; Chen JA; Caronia-Brown G; Cherepanova N; Yun B; Joksimovic M; Rock J; Harfe BD; Johnson R; Awatramani R. 2013. An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool. PLoS Genet 9(12):e1003973. PubMed: 24348261MGI: J:207519
- Aoto K; Trainor PA. 2015. Co-ordinated brain and craniofacial development depend upon Patched1/XIAP regulation of cell survival. Hum Mol Genet 24(3):698-713. PubMed: 25292199MGI: J:218093
- Bell SM; Zhang L; Mendell A; Xu Y; Haitchi HM; Lessard JL; Whitsett JA. 2011. Kruppel-like factor 5 is required for formation and differentiation of the bladder urothelium. Dev Biol 358(1):79-90. PubMed: 21803035MGI: J:176604
- Bell SM; Zhang L; Xu Y; Besnard V; Wert SE; Shroyer N; Whitsett JA. 2013. Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium. Dev Biol 375(2):128-39. PubMed: 23266329MGI: J:194289
- Belle M; Godefroy D; Dominici C; Heitz-Marchaland C; Zelina P; Hellal F; Bradke F; Chedotal A. 2014. A simple method for 3D analysis of immunolabeled axonal tracts in a transparent nervous system. Cell Rep 9(4):1191-201. PubMed: 25456121MGI: J:218756
- Bodea GO; Spille JH; Abe P; Andersson AS; Acker-Palmer A; Stumm R; Kubitscheck U; Blaess S. 2014. Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system. Development 141(3):661-73. PubMed: 24449842MGI: J:208337
- Boucherat O; Landry-Truchon K; Berube-Simard FA; Houde N; Beuret L; Lezmi G; Foulkes WD; Delacourt C; Charron J; Jeannotte L. 2015. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis. Development 142(17):2981-95. PubMed: 26329601MGI: J:239777
- Boucherat O; Nadeau V; Berube-Simard FA; Charron J; Jeannotte L. 2014. Crucial requirement of ERK/MAPK signaling in respiratory tract development. Development 141(16):3197-211. PubMed: 25100655MGI: J:214083
- 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: 18272593MGI: J:132152
- Chang DR; Martinez Alanis D; Miller RK; Ji H; Akiyama H; McCrea PD; Chen J. 2013. Lung epithelial branching program antagonizes alveolar differentiation. Proc Natl Acad Sci U S A 110(45):18042-51. PubMed: 24058167MGI: J:202949
- Chang H; Smallwood PM; Williams J; Nathans J. 2016. The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation. Dev Biol 409(1):181-93. PubMed: 26517967MGI: J:228792
- Choi KS; Harfe BD. 2011. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs. Proc Natl Acad Sci U S A 108(23):9484-9. PubMed: 21606373MGI: J:173333
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- Gritli-Linde A; Hallberg K; Harfe BD; Reyahi A; Kannius-Janson M; Nilsson J; Cobourne MT; Sharpe PT; McMahon AP; Linde A. 2007. Abnormal hair development and apparent follicular transformation to mammary gland in the absence of hedgehog signaling. Dev Cell 12(1):99-112. PubMed: 17199044MGI: J:117334
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- Haara O; Fujimori S; Schmidt-Ullrich R; Hartmann C; Thesleff I; Mikkola ML. 2011. Ectodysplasin and Wnt pathways are required for salivary gland branching morphogenesis. Development 138(13):2681-91. PubMed: 21652647MGI: J:173573
- Harfe BD; McManus MT; Mansfield JH; Hornstein E; Tabin CJ. 2005. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102(31):10898-903. PubMed: 16040801MGI: J:100475
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- Hayes L; Ralls S; Wang H; Ahn S. 2013. Duration of Shh signaling contributes to mDA neuron diversity. Dev Biol 374(1):115-26. PubMed: 23201023MGI: J:193109
- Herriges JC; Verheyden JM; Zhang Z; Sui P; Zhang Y; Anderson MJ; Swing DA; Zhang Y; Lewandoski M; Sun X. 2015. FGF-Regulated ETV Transcription Factors Control FGF-SHH Feedback Loop in Lung Branching. Dev Cell 35(3):322-32. PubMed: 26555052MGI: J:240020
- Higashiyama H; Ozawa A; Sumitomo H; Uemura M; Fujino K; Igarashi H; Imaimatsu K; Tsunekawa N; Hirate Y; Kurohmaru M; Saijoh Y; Kanai-Azuma M; Kanai Y. 2017. Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia. Development 144(10):1906-1917. PubMed: 28432216MGI: J:241569
- Hsu YC; Li L; Fuchs E. 2014. Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell 157(4):935-49. PubMed: 24813615MGI: J:214395
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- Joo JH; Taxter TJ; Munguba GC; Kim YH; Dhaduvai K; Dunn NW; Degan WJ; Oh SP; Sugrue SP. 2010. Pinin modulates expression of an intestinal homeobox gene, Cdx2, and plays an essential role for small intestinal morphogenesis. Dev Biol 345(2):191-203. PubMed: 20637749MGI: J:164807
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- Kasberg AD; Brunskill EW; Steven Potter S. 2013. SP8 regulates signaling centers during craniofacial development. Dev Biol 381(2):312-23. PubMed: 23872235MGI: J:200761
- Kim BM; Mao J; Taketo MM; Shivdasani RA. 2007. Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology 133(2):529-38. PubMed: 17681174MGI: J:128278
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- King P; Paul A; Laufer E. 2009. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc Natl Acad Sci U S A 106(50):21185-90. PubMed: 19955443MGI: J:155826
- Kittappa R; Chang WW; Awatramani RB; McKay RD. 2007. The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age. PLoS Biol 5(12):e325. PubMed: 18076286MGI: J:130846
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