Description

Strain Information

Former Names 129-Shhtm2Amc/J    (Changed: 06-APR-11 ) 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 N20F?+21 (27-NOV-11) Generation Definitions   Donating Investigator Andrew P McMahon,   University of Southern California

Description
Mice that are homozygous for the Shh^tm2Amc targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This conditional mutant contains two loxP sites flanking exon 2 of the targeted allele. Cre-mediated recombination excises exon 2 and some surrounding intronic sequence, generating a null allele. When the conditional mutant is crossed with a ubiquitously-expressing Cre recombinase carrier to remove Shh activity in the early embryo, the resulting phenotype resembles the Shh null mutation. These conditional mutant mice may be mated to strains expressing Cre recombinase to study the effects of temporal and tissue-specific ablation of the targeted allele. This mutant mouse strain represents a model that may be useful in studies of developmental defects resulting from disruption of Shh-dependent pathways.

When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element (see Stock No. 006224, 006234, 006244) and a strain expressing a tetracycline-controlled activator protein in the lung and respiratory epithelium (see Stock No. 006225), this mutant mouse strain provides an inducible model for use in studies of hedgehog signaling in respiratory system development.

When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the skin and dental epithelium (Stock No. 004782), this mutant mouse strain may be useful in studies of hedgehog signaling and cell proliferation in the dental epithelium.

When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the mesonephric duct and its developmental derivatives (Stock No. 004692), this mutant mouse strain may be useful in studies of hedgehog signalling and cell proliferation/differentiation in mesenchymal cells of the kidney.

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 of hedgehog signaling in cortical interneurons.

Development
The original recombinant allele contained a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter with flanking loxP sites. The PGK-Neo cassette was removed by Cre-mediated recombination in ES cells to produce the Shh conditional allele. In the Shh conditional allele, exon 2 is flanked by loxP sites. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were backcrossed to 129X1 mice. The donating investigator reports that these mice were intercrossed for 20 generations to the same and then maintained as a homozygous colony prior to arrival at The Jackson Laboratory.

A 140 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory in 2010 revealed these mice have large regions of C57BL/6-allele type regions throughout the genome. 16/140 markers were homozygous for C57BL/6-allele type on chromosome 5 (84.1-100.9-120.6 Mb), chromosome 8 (3.1-20.1 Mb and 54.1-73.2-93.1-109.9 Mb), chromosome 10 (60.1 Mb), chromosome 11 (63.5 Mb), chromosome 12 (34.6-54.3 Mb), and chromosome 16 (25.2 Mb and 64.1-84.3 Mb). Positions separated by a dash (-) indicated consecutive markers (although it is not determined if these regions are composed entirely of C57BL/6-type alleles). One marker on chromosome 16 was segregating for C57BL/6- and 129-allele type (45.1 Mb). Interestingly, the C57BL/6-allele type region on chromosome 8 contained one marker homozygous for 129-allele type at 35.0 Mb.

Control Information

	Control
	000691 129X1/SvJ	(approximate)
	101043 B6129SF1/J	(approximate)
Considerations for Choosing Controls

Related Strains

Facebase: models

007664	129S-Efnb1tm1Sor/J
000646	A/J
000647	A/WySnJ
005709	B6.129-Skitm1Cco/J
002619	B6.129-Tgfb3tm1Doe/J
007453	B6.129P2(Cg)-Dhcr7tm1Gst/J
010525	B6.129S-Notch2tm3Grid/J
010616	B6.129S1-Jag1tm1Grid/J
010546	B6.129S1-Jag2tm1Grid/J
010620	B6.129S1-Notch2tm1Grid/J
009387	B6.129S1-Osr1tm1Jian/J
009386	B6.129S1-Osr2tm1Jian/J
010621	B6.129S1-Snai1tm2.1Grid/J
010617	B6.129S1-Snai2tm1Grid/J
003865	B6.129S2-Itgavtm1Hyn/J
003755	B6.129S4-Meox2tm1(cre)Sor/J
016902	B6.129S5-Irf6Gt(OST398253)Lex/J
003336	B6.129S7-Cdkn1ctm1Sje/J
012843	B6.129X1(Cg)-Slc32a1tm1.1Bgc/J
000026	B6.C3-Gli3Xt-J/J
004275	B6.Cg-Fignfi/Frk
012844	B6.Cg-Gad1tm1.1Bgc/J
006382	B6;129-Casktm1Sud/J
002711	B6;129-Gabrb3tm1Geh/J
012603	B6;129-Tgfbr2tm1Karl/J
010618	B6;129S-Jag1tm2Grid/J
010686	B6;129S-Snai1tm2Grid/J
009389	B6;129S1-Bambitm1Jian/J
010619	B6;129S1-Lfngtm1Grid/J
010547	B6;129S1-Notch3tm1Grid/J
010544	B6;129S1-Notch4tm1Grid/J
010722	B6;129S1-Snai2tm2Grid/J
012463	B6;129S4-Foxd1tm1(GFP/cre)Amc/J
003277	B6;129S7-Acvr2atm1Zuk/J
002788	B6;129S7-Fsttm1Zuk/J
002990	B6;129S7-Inhbatm1Zuk/J
000523	B6By.Cg-Eh/J
000278	B6C3Fe a/a-Papss2bm Hps1ep Hps6ru/J
000515	B6CBACa Aw-J/A-SfnEr/J
001434	C3HeB/FeJ x STX/Le-Mc1rE-so Gli3Xt-J Zeb1Tw/J
000252	DC/LeJ
005057	FVB.129-Kcnj2tm1Swz/J
012655	FVB.A-Irf6clft1/BeiJ
013100	FVB.C-Prdm16csp1/J
017437	FVB/N-Ckap5TgTn(sb-cHS4,Tyr)2320F-1Ove/J
017438	FVB/N-MidnTg(Tyr)2261EOve/J
017609	FVB/N-Rr16Tn(sb-Tyr)1HCebOve/J
017598	FVB/N-Sdccag8Tn(sb-Tyr)2161B.CA1C2Ove/J
017608	FVB/N-Skor2Tn(sb-Tyr)1799B.CA7BOve/J
017436	FVB/N-Tapt1TgTn(sb-cHS4,Tyr)2508GOve/J
016870	FVB/NJ-Ap2b1Tg(Tyr)427Ove/EtevJ
017434	FVB;B6-Cramp1lTgTn(sb-rtTA,Tyr)2447AOve/J
017594	FVB;B6-Eya4TgTn(Prm1-sb10,sb-Tyr)1739AOve/J
017435	FVB;B6-SlmapTn(sb-rtTA)2426B.SB4Ove/J
003318	STOCK Shhtm1Amc/J
003102	STOCK Tgfb2tm1Doe/J
018624	STOCK Tgfb3tm2(Tgfb1)Vk/J
008469	STOCK Wnt9btm1.2Amc/J

View Facebase: models     (58 strains)

Strains carrying other alleles of Shh

000214	B10.D2/nSn-ShhHx/J
005623	B6.129S6-Shhtm2(cre/ERT2)Cjt/J
008466	B6.129X1(Cg)-Shhtm6Amc/J
005622	B6.Cg-Shhtm1(EGFP/cre)Cjt/J
011031	B6;129S4-Shhtm1.1Rseg/J
003318	STOCK Shhtm1Amc/J

View Strains carrying other alleles of Shh     (6 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Holoprosencephaly 3; HPE3   (SHH) Microphthalmia, Isolated, with Coloboma 5; MCOPCB5   (SHH) Schizencephaly   (SHH) Solitary Median Maxillary Central Incisor; SMMCI   (SHH)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Shh^tm1Amc/Shh^tm2Amc Tg(KRT14-cre)1Amc/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA   (conditional)

• mortality/aging
• complete neonatal lethality
  • mutant newborns die within a day after birth   (MGI Ref ID J:65294)
• craniofacial phenotype
• abnormal ameloblast morphology
  • at birth, functional odontoblast and ameloblast layers are present but display abnormal polarity and cellular architecture   (MGI Ref ID J:65294)
  • when early tooth rudiments (13.5-15.5 dpc) are transplanted under kidney capsules of nude mice, enamel and dentin matrices are deposited in spite of absent ameloblast elongation and odontoblast disorganization   (MGI Ref ID J:65294)
• abnormal cranium morphology
  • at birth, mutant pups display flattened skulls   (MGI Ref ID J:65294)
• • abnormal nasal bone morphology
    • at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced   (MGI Ref ID J:65294)
  • absent alveolar process
    • mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent   (MGI Ref ID J:65294)
• abnormal dentin morphology
  • in grafts of early tooth rudiments (13.5-15.5 dpc), dentin deposits are deposited but crown formation is incomplete and resulting teeth are small and abnormally shaped   (MGI Ref ID J:65294)
• abnormal enamel morphology
  • at 14.5 dpc, the outer enamel epithelium of the lingual side is severely reduced and the lingual inner enamel epithelium has not invaginated, suggesting impaired crown formation   (MGI Ref ID J:65294)
  • when early tooth rudiments (13.5-15.5 dpc) are transplanted under kidney capsules of nude mice, enamel matrix is secreted but crown formation is incomplete and resulting teeth are small and abnormally shaped   (MGI Ref ID J:65294)
• abnormal incisor morphology
  • at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla   (MGI Ref ID J:65294)
  • mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted   (MGI Ref ID J:65294)
• abnormal molar crown morphology
  • mandibular molars display a single irregular cusp; additional cusp formation is disrupted   (MGI Ref ID J:65294)
• arrest of tooth development
  • at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology   (MGI Ref ID J:65294)
• cleft secondary palate
  • 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart   (MGI Ref ID J:90909)
• • abnormal palatal shelf fusion at midline
    • the rudimentary palatal shelves are spaced widely apart   (MGI Ref ID J:90909)
  • palatal shelf hypoplasia
    • the palatal shelves fail to develop beyond rudimentary processes   (MGI Ref ID J:90909)
• growth retardation of incisors
  • at birth, mandibular incisors are more developmentally advanced relative to mandibular molars   (MGI Ref ID J:65294)
• growth retardation of molars
  • at birth, mandibular molars are less developmentally advanced relative to mandibular incisors   (MGI Ref ID J:65294)
• small molars
  • at birth, mutant pups display small and abnormally shaped first molars in both the mandible and maxilla   (MGI Ref ID J:65294)
  • maxillary molars are less affected than mandibular molars which are 25% of normal size   (MGI Ref ID J:65294)
  • although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed   (MGI Ref ID J:65294)
• skeleton phenotype
• *normal* skeleton phenotype
  • at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length   (MGI Ref ID J:65294)
• • abnormal cranium morphology
    • at birth, mutant pups display flattened skulls   (MGI Ref ID J:65294)
  • • abnormal nasal bone morphology
      • at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced   (MGI Ref ID J:65294)
    • absent alveolar process
      • mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent   (MGI Ref ID J:65294)
• vision/eye phenotype
• eyelids open at birth   (MGI Ref ID J:65294)
• respiratory system phenotype
• aerophagia
  • at birth, mutant pups are observed gulping air   (MGI Ref ID J:65294)
• digestive/alimentary phenotype
• cleft secondary palate
  • 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart   (MGI Ref ID J:90909)
• • abnormal palatal shelf fusion at midline
    • the rudimentary palatal shelves are spaced widely apart   (MGI Ref ID J:90909)
  • palatal shelf hypoplasia
    • the palatal shelves fail to develop beyond rudimentary processes   (MGI Ref ID J:90909)
• integument phenotype
• absent vibrissae   (MGI Ref ID J:65294)

Shh^tm2Amc/Shh^tm2Amc Tg(Nes-cre)1Kln/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL   (conditional)

• mortality/aging
• complete postnatal lethality
  • death by P15   (MGI Ref ID J:102950)
• growth/size phenotype
• decreased body size
  • animals are smaller than littermates, but are postnatally viable and have relatively normal gross morphology   (MGI Ref ID J:147427)
• postnatal growth retardation
  • marked reduction in growth by the second postnatal week   (MGI Ref ID J:102950)
• craniofacial phenotype
• microcephaly   (MGI Ref ID J:102950)
• nervous system phenotype
• abnormal brain interneuron morphology
  • reductions of somatostatin- and parvalbumin-expressing interneurons in somatosensory cortex   (MGI Ref ID J:102950)
  • somatostatin- and Npy-expressing interneurons are also reduced in the striatum   (MGI Ref ID J:102950)
• abnormal medial ganglionic eminence morphology
  • reduced interneuron fate determining gene Nkx2.1 expression in progenitors of the medial ganglionic eminence (MGE) cells in S-phase   (MGI Ref ID J:102950)
  • a subtle disruption of MGE patterning indicated by reduction of Gli1 and Nkx6.2 expression is observed   (MGI Ref ID J:102950)
  • however, other aspects of MGE progenitor identity are maintained   (MGI Ref ID J:102950)
• abnormal thalamus morphology
  • thalamus organization is disrupted in mutants based on molecular marker analysis   (MGI Ref ID J:147427)
• decreased brain size
  • 10% decrease in cortical thickness at P12   (MGI Ref ID J:102950)
  • animals display slightly smaller brain size than control littermates, but overall morphology of brain is relatively normal   (MGI Ref ID J:147427)
• seizures
  • pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week   (MGI Ref ID J:102950)
• behavior/neurological phenotype
• seizures
  • pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week   (MGI Ref ID J:102950)

Shh^tm2Amc/Shh^tm2Amc Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0

        involves: FVB/N   (conditional)

• mortality/aging
• complete neonatal lethality
  • mutants die shortly after birth when doxycycline is administered throughout gestation   (MGI Ref ID J:91723)
  • in the absence of doxycycline mutants are viable   (MGI Ref ID J:91723)
• respiratory system phenotype
• abnormal lung morphology
  • lung and airway malformations are seen when doxycycline exposure occurs between E0.5 and E13.5   (MGI Ref ID J:91723)
  • doxycycline exposure after E13.5 does not result in any pulmonary or extrapulmonary abnormalities   (MGI Ref ID J:91723)
• • abnormal bronchus morphology
    • peripheral tubule dilation is seen after doxycycline exposure   (MGI Ref ID J:91723)
  • lung cysts
    • cysts that contain neuroepithelial cells are seen in the peripheral lung tissue   (MGI Ref ID J:91723)
  • pulmonary hypoplasia
    • lungs are hypoplastic when doxycycline is administered throughout gestation   (MGI Ref ID J:91723)
• abnormal trachea morphology
  • tracheal abnormalities are seen   (MGI Ref ID J:91723)
  • doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities   (MGI Ref ID J:91723)
• • abnormal tracheal cartilage morphology
    • the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure   (MGI Ref ID J:91723)
  • • decreased tracheal cartilage ring number
      • fewer cartilaginous rings are seen after doxycycline exposure   (MGI Ref ID J:91723)
• abnormal tracheal-bronchial branching morphogenesis
  • branching morphogenesis is abnormal   (MGI Ref ID J:91723)
• skeleton phenotype
• abnormal tracheal cartilage morphology
  • the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure   (MGI Ref ID J:91723)
• • decreased tracheal cartilage ring number
    • fewer cartilaginous rings are seen after doxycycline exposure   (MGI Ref ID J:91723)

Shh^tm1Amc/Shh^tm2Amc Tg(Hoxb7-cre)13Amc/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6   (conditional)

• renal/urinary system phenotype
• abnormal kidney inner medulla morphology
  • at 4 months of age, most of the inner medulla is lost in hydronephric kidneys   (MGI Ref ID J:79481)
• abnormal kidney outer medulla inner stripe morphology
  • at 4 months of age, most of the inner stripe of the outer medulla is lost in hydronephric kidneys   (MGI Ref ID J:79481)
• abnormal renal glomerulus morphology
  • at the newborn stage, cortical glomerular density is increased by 24% while glomerular density of the whole kidney is increased by 26% relative to that in wild-type controls   (MGI Ref ID J:79481)
  • however, no gross differences in glomerular size are observed   (MGI Ref ID J:79481)
• • decreased renal glomerulus number
    • newborn mice exhibit a 40% reduction in glomerular number   (MGI Ref ID J:79481)
• abnormal ureter development
  • at E14.5, fewer mesenchymal cells line the ureteral epithelium relative to wild-type controls   (MGI Ref ID J:79481)
  • at E14.5, the mitotic index of the proximal and distal ureter mesenchyme is ~50% of that in wild-type controls, indicating reduced cell proliferation   (MGI Ref ID J:79481)
  • however, no differences in ureteral mesenchyme apoptosis are observed by TUNEL analysis   (MGI Ref ID J:79481)
• abnormal ureter smooth muscle morphology
  • a delay in smooth muscle differentiation is observed along the proximodistal axis of the ureter   (MGI Ref ID J:79481)
  • at E15.0, no smooth muscle alpha-actin protein (SMA), an early marker of smooth muscle differentiation, is detected at any axial level of the ureter, unlike in wild-type embryos where SMA is detected in the proximal ureter   (MGI Ref ID J:79481)
  • at the newborn stage, SMA is detected in the proximal ureter but, in contrast to wild-type controls, almost no SMA is detected in the distal-most part of the ureter, closest to the bladder   (MGI Ref ID J:79481)
  • in addition, mesenchymal cells in the distal ureter are not as condensed as those in wild-type controls   (MGI Ref ID J:79481)
• hydronephrosis
  • at 4 months of age, 50% of mice exhibit hydronephrosis   (MGI Ref ID J:79481)
  • however, no hydronephrosis is detected in newborn pups   (MGI Ref ID J:79481)
• hydroureter
  • newborn mice exhibit prominent hydroureter, usually more severe in the proximal region   (MGI Ref ID J:79481)
• kidney cortex hypoplasia
  • at the newborn stage, cortical volume is reduced by 51%   (MGI Ref ID J:79481)
• kidney medulla hypoplasia
  • at the newborn stage, medullary volume is reduced by 46%   (MGI Ref ID J:79481)
• short ureter
  • at E14.5, ureter length is ~21% shorter than in wild-type controls   (MGI Ref ID J:79481)
• small kidney
  • neonatal kidneys are 52% smaller than wild-type kidneys   (MGI Ref ID J:79481)
• • renal hypoplasia   (MGI Ref ID J:79481)

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cre-lox System
      loxP-flanked Sequences

Shh^tm2Amc related

Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines
Oncogenes

Cell Biology Research
Genes Regulating Growth and Proliferation

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
Eye Defects
Growth Defects
Internal/Organ Defects
Neural Tube Defects
Neurodevelopmental Defects
Postnatal Lethality
Skeletal Defects

Neurobiology Research
Neural Tube Defects
Neurodevelopmental Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Shhtm2Amc
Allele Name		targeted mutation 2, Andrew P McMahon
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		ShhC-NShh; ShhCo; Shhc; Shhf; Shhflox; Shhflx; Shhlox;
Mutation Made By		Dr. Paula Lewis,   AstraZeneca, R&D Boston
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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		LoxP sites were inserted into intronic sequences flanking exon 2. This mutation has no effect on the normal function of this gene. [MGI Ref ID J:65294]

Genotyping

Genotyping Information

Genotyping Protocols

Shh^tm2Amc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lewis PM; Dunn MP; McMahon JA; Logan M; Martin JF; St-Jacques B; McMahon AP. 2001. Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell 105(5):599-612. [PubMed: 11389830]  [MGI Ref ID J:69771]

Additional References

Aoto K; Nishimura T; Eto K; Motoyama J. 2002. Mouse GLI3 Regulates Fgf8 Expression and Apoptosis in the Developing Neural Tube, Face, and Limb Bud. Dev Biol 251(2):320-32. [PubMed: 12435361]  [MGI Ref ID J:80177]

Machold R; Hayashi S; Rutlin M; Muzumdar MD; Nery S; Corbin JG; Gritli-Linde A; Dellovade T; Porter JA; Rubin LL; Dudek H; McMahon AP; Fishell G. 2003. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39(6):937-50. [PubMed: 12971894]  [MGI Ref ID J:85603]

Wang YP; Dakubo G; Howley P; Campsall KD; Mazarolle CJ; Shiga SA; Lewis PM; McMahon AP; Wallace VA. 2002. Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cells. Nat Neurosci 5(9):831-2. [PubMed: 12195432]  [MGI Ref ID J:78708]

Shh^tm2Amc related

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: 20724449]  [MGI Ref ID J:168361]

Balmer CW; LaMantia AS. 2004. Loss of Gli3 and Shh function disrupts olfactory axon trajectories. J Comp Neurol 472(3):292-307. [PubMed: 15065125]  [MGI Ref ID J:109287]

Bluske KK; Kawakami Y; Koyano-Nakagawa N; Nakagawa Y. 2009. Differential activity of Wnt/beta-catenin signaling in the embryonic mouse thalamus. Dev Dyn 238(12):3297-3309. [PubMed: 19924825]  [MGI Ref ID J:154363]

Bluske KK; Vue TY; Kawakami Y; Taketo MM; Yoshikawa K; Johnson JE; Nakagawa Y. 2012. beta-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus. Development 139(15):2692-702. [PubMed: 22745311]  [MGI Ref ID J:185651]

Cameron DA; Pennimpede T; Petkovich M. 2009. Tulp3 is a critical repressor of mouse hedgehog signaling. Dev Dyn 238(5):1140-9. [PubMed: 19334287]  [MGI Ref ID J:148411]

Ching S; Vilain E. 2009. Targeted disruption of Sonic Hedgehog in the mouse adrenal leads to adrenocortical hypoplasia. Genesis 47(9):628-37. [PubMed: 19536807]  [MGI Ref ID J:155992]

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: 21606373]  [MGI Ref ID J:173333]

Choi KS; Lee C; Harfe BD. 2012. Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs. Mech Dev 129(9-12):255-62. [PubMed: 22841806]  [MGI Ref ID J:188787]

Dakubo GD; Beug ST; Mazerolle CJ; Thurig S; Wang Y; Wallace VA. 2008. Control of glial precursor cell development in the mouse optic nerve by sonic hedgehog from retinal ganglion cells. Brain Res 1228:27-42. [PubMed: 18625210]  [MGI Ref ID J:139978]

Dakubo GD; Wang YP; Mazerolle C; Campsall K; McMahon AP; Wallace VA. 2003. Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development. Development 130(13):2967-80. [PubMed: 12756179]  [MGI Ref ID J:83530]

Dassule HR; Lewis P; Bei M; Maas R; McMahon AP. 2000. Sonic hedgehog regulates growth and morphogenesis of the tooth Development 127(22):4775-85. [PubMed: 11044393]  [MGI Ref ID J:65294]

Dessaud E; Ribes V; Balaskas N; Yang LL; Pierani A; Kicheva A; Novitch BG; Briscoe J; Sasai N. 2010. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biol 8(6):e1000382. [PubMed: 20532235]  [MGI Ref ID J:161598]

Di Meglio T; Kratochwil CF; Vilain N; Loche A; Vitobello A; Yonehara K; Hrycaj SM; Roska B; Peters AH; Eichmann A; Wellik D; Ducret S; Rijli FM. 2013. Ezh2 orchestrates topographic migration and connectivity of mouse precerebellar neurons. Science 339(6116):204-7. [PubMed: 23307742]  [MGI Ref ID J:193244]

Economou AD; Ohazama A; Porntaveetus T; Sharpe PT; Kondo S; Basson MA; Gritli-Linde A; Cobourne MT; Green JB. 2012. Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate. Nat Genet 44(3):348-51. [PubMed: 22344222]  [MGI Ref ID J:181644]

El-Hashash AH; Al Alam D; Turcatel G; Bellusci S; Warburton D. 2011. Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. Dev Biol 350(1):112-26. [PubMed: 21129374]  [MGI Ref ID J:170236]

El-Jaick KB; Powers SE; Bartholin L; Myers KR; Hahn J; Orioli IM; Ouspenskaia M; Lacbawan F; Roessler E; Wotton D; Muenke M. 2007. Functional analysis of mutations in TGIF associated with holoprosencephaly. Mol Genet Metab 90(1):97-111. [PubMed: 16962354]  [MGI Ref ID J:116565]

Ferri AL; Lin W; Mavromatakis YE; Wang JC; Sasaki H; Whitsett JA; Ang SL. 2007. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development 134(15):2761-9. [PubMed: 17596284]  [MGI Ref ID J:124122]

Flandin P; Zhao Y; Vogt D; Jeong J; Long J; Potter G; Westphal H; Rubenstein JL. 2011. Lhx6 and Lhx8 coordinately induce neuronal expression of Shh that controls the generation of interneuron progenitors. Neuron 70(5):939-50. [PubMed: 21658586]  [MGI Ref ID J:174967]

Goddeeris MM; Rho S; Petiet A; Davenport CL; Johnson GA; Meyers EN; Klingensmith J. 2008. Intracardiac septation requires hedgehog-dependent cellular contributions from outside the heart. Development 135(10):1887-95. [PubMed: 18441277]  [MGI Ref ID J:134643]

Goddeeris MM; Schwartz R; Klingensmith J; Meyers EN. 2007. Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development. Development 134(8):1593-604. [PubMed: 17344228]  [MGI Ref ID J:135134]

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: 17199044]  [MGI Ref ID J:117334]

Haraguchi R; Matsumaru D; Nakagata N; Miyagawa S; Suzuki K; Kitazawa S; Yamada G. 2012. The hedgehog signal induced modulation of bone morphogenetic protein signaling: an essential signaling relay for urinary tract morphogenesis. PLoS One 7(7):e42245. [PubMed: 22860096]  [MGI Ref ID J:189675]

Harwell CC; Parker PR; Gee SM; Okada A; McConnell SK; Kreitzer AC; Kriegstein AR. 2012. Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation. Neuron 73(6):1116-26. [PubMed: 22445340]  [MGI Ref ID J:183457]

Hayashi S; Lewis P; Pevny L; McMahon AP. 2002. Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain. Mech Dev 119 Suppl 1:S97-S101. [PubMed: 14516668]  [MGI Ref ID J:83040]

Huang CC; Liu C; Yao HH. 2012. Investigating the role of adrenal cortex in organization and differentiation of the adrenal medulla in mice. Mol Cell Endocrinol 361(1-2):165-71. [PubMed: 22580128]  [MGI Ref ID J:189572]

Huang CC; Miyagawa S; Matsumaru D; Parker KL; Yao HH. 2010. Progenitor cell expansion and organ size of mouse adrenal is regulated by sonic hedgehog. Endocrinology 151(3):1119-28. [PubMed: 20118198]  [MGI Ref ID J:168522]

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]

Huang X; Liu J; Ketova T; Fleming JT; Grover VK; Cooper MK; Litingtung Y; Chiang C. 2010. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc Natl Acad Sci U S A 107(18):8422-7. [PubMed: 20400693]  [MGI Ref ID J:160335]

Jacob J; Ferri AL; Milton C; Prin F; Pla P; Lin W; Gavalas A; Ang SL; Briscoe J. 2007. Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis. Nat Neurosci 10(11):1433-9. [PubMed: 17922007]  [MGI Ref ID J:128441]

Joksimovic M; Yun BA; Kittappa R; Anderegg AM; Chang WW; Taketo MM; McKay RD; Awatramani RB. 2009. Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis. Nat Neurosci 12(2):125-31. [PubMed: 19122665]  [MGI Ref ID J:146200]

Kim TH; Kim BM; Mao J; Rowan S; Shivdasani RA. 2011. Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development 138(15):3225-33. [PubMed: 21750033]  [MGI Ref ID J:180905]

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: 19955443]  [MGI Ref ID J:155826]

Komada M; Saitsu H; Kinboshi M; Miura T; Shiota K; Ishibashi M. 2008. Hedgehog signaling is involved in development of the neocortex. Development 135(16):2717-27. [PubMed: 18614579]  [MGI Ref ID J:138572]

Lan Y; Jiang R. 2009. Sonic hedgehog signaling regulates reciprocal epithelial-mesenchymal interactions controlling palatal outgrowth. Development 136(8):1387-96. [PubMed: 19304890]  [MGI Ref ID J:147277]

Lewis PM; Gritli-Linde A; Smeyne R; Kottmann A; McMahon AP. 2004. Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol 270(2):393-410. [PubMed: 15183722]  [MGI Ref ID J:92189]

Lin C; Fisher AV; Yin Y; Maruyama T; Veith GM; Dhandha M; Huang GJ; Hsu W; Ma L. 2011. The inductive role of Wnt-beta-Catenin signaling in the formation of oral apparatus. Dev Biol 356(1):40-50. [PubMed: 21600200]  [MGI Ref ID J:175262]

Lin C; Yin Y; Veith GM; Fisher AV; Long F; Ma L. 2009. Temporal and spatial dissection of Shh signaling in genital tubercle development. Development 136(23):3959-67. [PubMed: 19906863]  [MGI Ref ID J:158288]

Lin W; Metzakopian E; Mavromatakis YE; Gao N; Balaskas N; Sasaki H; Briscoe J; Whitsett JA; Goulding M; Kaestner KH; Ang SL. 2009. Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev Biol 333(2):386-96. [PubMed: 19607821]  [MGI Ref ID J:152413]

Machold R; Hayashi S; Rutlin M; Muzumdar MD; Nery S; Corbin JG; Gritli-Linde A; Dellovade T; Porter JA; Rubin LL; Dudek H; McMahon AP; Fishell G. 2003. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39(6):937-50. [PubMed: 12971894]  [MGI Ref ID J:85603]

Mao J; Kim BM; Rajurkar M; Shivdasani RA; McMahon AP. 2010. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 137(10):1721-9. [PubMed: 20430747]  [MGI Ref ID J:160363]

Mao J; McGlinn E; Huang P; Tabin CJ; McMahon AP. 2009. Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb. Dev Cell 16(4):600-6. [PubMed: 19386268]  [MGI Ref ID J:149478]

Mavromatakis YE; Lin W; Metzakopian E; Ferri AL; Yan CH; Sasaki H; Whisett J; Ang SL. 2011. Foxa1 and Foxa2 positively and negatively regulate Shh signalling to specify ventral midbrain progenitor identity. Mech Dev 128(1-2):90-103. [PubMed: 21093585]  [MGI Ref ID J:170258]

McNeill B; Mazerolle C; Bassett EA; Mears AJ; Ringuette R; Lagali P; Picketts DJ; Paes K; Rice D; Wallace VA. 2013. Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal. Hum Mol Genet 22(5):1005-16. [PubMed: 23201751]  [MGI Ref ID J:192563]

Miller LA; Wert SE; Clark JC; Xu Y; Perl AK; Whitsett JA. 2004. Role of Sonic hedgehog in patterning of tracheal-bronchial cartilage and the peripheral lung. Dev Dyn 231(1):57-71. [PubMed: 15305287]  [MGI Ref ID J:91723]

Miyagawa S; Matsumaru D; Murashima A; Omori A; Satoh Y; Haraguchi R; Motoyama J; Iguchi T; Nakagata N; Hui CC; Yamada G. 2011. The role of sonic hedgehog-gli2 pathway in the masculinization of external genitalia. Endocrinology 152(7):2894-903. [PubMed: 21586556]  [MGI Ref ID J:174885]

Miyagawa S; Moon A; Haraguchi R; Inoue C; Harada M; Nakahara C; Suzuki K; Matsumaru D; Kaneko T; Matsuo I; Yang L; Taketo MM; Iguchi T; Evans SM; Yamada G. 2009. Dosage-dependent hedgehog signals integrated with Wnt/{beta}-catenin signaling regulate external genitalia formation as an appendicular program. Development 136(23):3969-78. [PubMed: 19906864]  [MGI Ref ID J:154979]

Nielsen CM; Dymecki SM. 2010. Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus. Dev Biol 340(2):430-7. [PubMed: 20123094]  [MGI Ref ID J:160263]

Perez-Balaguer A; Puelles E; Wurst W; Martinez S. 2009. Shh dependent and independent maintenance of basal midbrain. Mech Dev 126(5-6):301-13. [PubMed: 19298856]  [MGI Ref ID J:149237]

Rice R; Spencer-Dene B; Connor EC; Gritli-Linde A; McMahon AP; Dickson C; Thesleff I; Rice DP. 2004. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. J Clin Invest 113(12):1692-700. [PubMed: 15199404]  [MGI Ref ID J:90909]

Sala FG; Del Moral PM; Tiozzo C; Alam DA; Warburton D; Grikscheit T; Veltmaat JM; Bellusci S. 2011. FGF10 controls the patterning of the tracheal cartilage rings via Shh. Development 138(2):273-82. [PubMed: 21148187]  [MGI Ref ID J:167739]

Seifert AW; Bouldin CM; Choi KS; Harfe BD; Cohn MJ. 2009. Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development. Development 136(23):3949-57. [PubMed: 19906862]  [MGI Ref ID J:154980]

Stottmann RW; Tran PV; Turbe-Doan A; Beier DR. 2009. Ttc21b is required to restrict sonic hedgehog activity in the developing mouse forebrain. Dev Biol 335(1):166-78. [PubMed: 19732765]  [MGI Ref ID J:154376]

Suzuki K; Yamaguchi Y; Villacorte M; Mihara K; Akiyama M; Shimizu H; Taketo MM; Nakagata N; Tsukiyama T; Yamaguchi TP; Birchmeier W; Kato S; Yamada G. 2009. Embryonic hair follicle fate change by augmented {beta}-catenin through Shh and Bmp signaling. Development 136(3):367-72. [PubMed: 19141668]  [MGI Ref ID J:144194]

Szabo NE; Zhao T; Cankaya M; Theil T; Zhou X; Alvarez-Bolado G. 2009. Role of neuroepithelial Sonic hedgehog in hypothalamic patterning. J Neurosci 29(21):6989-7002. [PubMed: 19474326]  [MGI Ref ID J:149516]

Szabo NE; Zhao T; Zhou X; Alvarez-Bolado G. 2009. The role of Sonic hedgehog of neural origin in thalamic differentiation in the mouse. J Neurosci 29(8):2453-66. [PubMed: 19244520]  [MGI Ref ID J:145945]

Taniguchi K; Anderson AE; Sutherland AE; Wotton D. 2012. Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway. PLoS Genet 8(2):e1002524. [PubMed: 22383895]  [MGI Ref ID J:183402]

Tian H; Jeong J; Harfe BD; Tabin CJ; McMahon AP. 2005. Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand. Development 132(1):133-42. [PubMed: 15576405]  [MGI Ref ID J:94270]

Tripathi P; Guo Q; Wang Y; Coussens M; Liapis H; Jain S; Kuehn MR; Capecchi MR; Chen F. 2010. Midline signaling regulates kidney positioning but not nephrogenesis through Shh. Dev Biol 340(2):518-27. [PubMed: 20152829]  [MGI Ref ID J:160256]

Tsiairis CD; McMahon AP. 2008. Disp1 regulates growth of mammalian long bones through the control of Ihh distribution. Dev Biol 317(2):480-5. [PubMed: 18395198]  [MGI Ref ID J:136115]

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]

Wang Y; Dakubo GD; Thurig S; Mazerolle CJ; Wallace VA. 2005. Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development 132(22):5103-13. [PubMed: 16236765]  [MGI Ref ID J:103124]

Wang YP; Dakubo G; Howley P; Campsall KD; Mazarolle CJ; Shiga SA; Lewis PM; McMahon AP; Wallace VA. 2002. Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cells. Nat Neurosci 5(9):831-2. [PubMed: 12195432]  [MGI Ref ID J:78708]

Xu Q; Wonders CP; Anderson SA. 2005. Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon. Development 132(22):4987-98. [PubMed: 16221724]  [MGI Ref ID J:102950]

Yu J; Carroll TJ; McMahon AP. 2002. Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development 129(22):5301-12. [PubMed: 12399320]  [MGI Ref ID J:79481]

Yu K; McGlynn S; Matise MP. 2013. Floor plate-derived sonic hedgehog regulates glial and ependymal cell fates in the developing spinal cord. Development 140(7):1594-604. [PubMed: 23482494]  [MGI Ref ID J:194893]

Zhao L; Zevallos SE; Rizzoti K; Jeong Y; Lovell-Badge R; Epstein DJ. 2012. Disruption of SoxB1-dependent Sonic hedgehog expression in the hypothalamus causes septo-optic dysplasia. Dev Cell 22(3):585-96. [PubMed: 22421044]  [MGI Ref ID J:182725]

Zhu J; Mackem S. 2011. Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen. Dev Dyn 240(5):1303-10. [PubMed: 21509901]  [MGI Ref ID J:170964]

Zhu J; Nakamura E; Nguyen MT; Bao X; Akiyama H; Mackem S. 2008. Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud. Dev Cell 14(4):624-32. [PubMed: 18410737]  [MGI Ref ID J:135157]

Zhu J; Nguyen MT; Nakamura E; Yang J; Mackem S. 2012. Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway. Genesis 50(2):102-11. [PubMed: 21913308]  [MGI Ref ID J:187873]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together. Coat color expected from breeding is Agouti.
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

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• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000691 129X1/SvJ	(approximate)
	101043 B6129SF1/J	(approximate)
Considerations for Choosing Controls
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.

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