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Strain Name:

STOCK Shhtm1Amc/J

Stock Number:

003318

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Genes & Alleles   Shh;   Shhtm1Amc;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Andrew McMahon,   Harvard University
GenerationN1F?+4p+N1p (09-NOV-05)

Appearance
agouti
Related Genotype: A/?

black
Related Genotype: a/a

Strain Description
Mice homozygous for the Shhtm1Amc targeted mutation display early defects in the establishment and maintenance of midline structures. These defects result from the critical role the Sonic hedgehog (Shh) gene plays in the patterning patterning of vertebrate embryonic tissues, including the brain and spinal cord, the axial skeleton and the limbs. Defects are also observed in all tissues, confirming the proposed role of SHH proteins as an extracellular signal required for the tissue-organizing properties of several vertebrate patterning centers.

When bred to a strain with loxP sites inserted into the same targeted allele (Stock No. 004293) 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 signalling and cell proliferation in the dental epithelium.

Mammalian Phenotype Terms assigned by genotype

Shhtm1Amc/Shhtm1Amc

        STOCK Shhtm1Amc/J
  • digestive/alimentary phenotype
  • abnormal submandibular gland morphology (MGI Ref ID J:89200)
    • at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG)
    • at E18.5, homozygotes display a slightly larger but severely pedomorphic dysplastic SMG consisting of largely undifferentiated epithelium with very few branches surrounded by undifferentiated mesenchyme (reminiscent of the Pseudoglandular stage at ~E14)
    • in vitro, Pseudoglandular (E14) stage SMG primordia cultured in the presence of Shh show a ~2-fold increase in epithelial branching compared with Initial Bud (E13) stage primordia, indicating a stage-specific difference in Shh-stimulated branching
    • cyclopamine-treated explants show a marked reduction in branching and epithelial cell proliferation; notably FGF8-supplemented explants exhibit a significant 58% increase in branching morphogenesis compared with cyclopamine treatment alone
  • endocrine/exocrine gland phenotype
  • abnormal submandibular gland morphology (MGI Ref ID J:89200)
    • at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG)
    • at E18.5, homozygotes display a slightly larger but severely pedomorphic dysplastic SMG consisting of largely undifferentiated epithelium with very few branches surrounded by undifferentiated mesenchyme (reminiscent of the Pseudoglandular stage at ~E14)
    • in vitro, Pseudoglandular (E14) stage SMG primordia cultured in the presence of Shh show a ~2-fold increase in epithelial branching compared with Initial Bud (E13) stage primordia, indicating a stage-specific difference in Shh-stimulated branching
    • cyclopamine-treated explants show a marked reduction in branching and epithelial cell proliferation; notably FGF8-supplemented explants exhibit a significant 58% increase in branching morphogenesis compared with cyclopamine treatment alone

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Shhtm1Amc/Shhtm1Amc

        Background Not Specified
  • lethality-prenatal/perinatal
  • neonatal lethality (MGI Ref ID J:91723)
    • homozygous mutants die shortly after birth
  • digestive/alimentary phenotype
  • abnormal tracheal-esophageal septation (MGI Ref ID J:91723)
    • a single tracheal-esophageal tube lacking any cartilaginous rings is seen
    • this tube is lined with stratified squamous epithelium dorsally and columnar airway epithelium ventrally
  • small stomach (MGI Ref ID J:98520)
    • reduced stomach size, particularly in the fore-stomach, at E12.5
  • respiratory system phenotype
  • abnormal bronchus morphology (MGI Ref ID J:91723)
    • peripheral tubules are absent
  • abnormal pharynx morphology (MGI Ref ID J:91723)
    • the pharynx is closed anteriorly
  • abnormal tracheal-bronchial branching morphogenesis (MGI Ref ID J:91723)
    • branching morphogenesis is impaired with the single tracheal-esophageal tube connected to the proximal and peripheral lung structures
  • abnormal tracheal-esophageal septation (MGI Ref ID J:91723)
    • a single tracheal-esophageal tube lacking any cartilaginous rings is seen
    • this tube is lined with stratified squamous epithelium dorsally and columnar airway epithelium ventrally
  • absent tracheal cartilage rings (MGI Ref ID J:91723)
    • the cartilaginous rings that normal surround the trachea are absent
  • pulmonary hypoplasia (MGI Ref ID J:91723)
    • lungs are severely hypoplastic
    • the anterior closed pharynx connects to a posteroir bilobed lung in which the central airway is surrounded only by rudimentary peripheral saccules
  • skeleton phenotype
  • absent tracheal cartilage rings (MGI Ref ID J:91723)
    • the cartilaginous rings that normal surround the trachea are absent

Shhtm1Amc/Shhtm1Amc

        involves: 129/Sv * C57BL/6J * CBA/J
  • lethality-prenatal/perinatal
  • perinatal lethality (MGI Ref ID J:50050)
    • none of the homozygotes surviving to term live beyond this time
  • prenatal lethality (MGI Ref ID J:50050)
    • only ~50% of homozygotes survive to term
  • skin/coat/nails phenotype
  • abnormal dermal layer morphology (MGI Ref ID J:50050)
    • skin grafts of mutant skin transplanted onto nude mice exhibit a reduced dermal fat layer
  • abnormal hair follicle morphology (MGI Ref ID J:50050)
    • at 15.5 dpc, mutant hair follicles form a smaller hair plug; however, epidermal expansion into the dermis and dermal condensation of mesenchyme at the base of the hair plug occur normally
    • at 15.5 dpc, wild-type hair follicles have progressed to stage 2, whereas mutant follicles at still at stage 1 or 0
    • abnormal dermal papilla (MGI Ref ID J:50050)
      • mutant skin displays only a rudimentary dermal papilla, indicating abnormal epithelial-mesenchymal interactions
    • abnormal hair follicle development (MGI Ref ID J:50050)
      • homozygotes display delayed hair folliculoenesis: embryonic follicles are arrested shortly after induction and fail to progress beyond stage 2
      • at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type; no difference is observed in apoptosis
    • abnormal hair follicle orientation (MGI Ref ID J:50050)
      • mutant hair buds fail to exhibit an obvious polarity; in contrast, wild-type follicles show a typical polarized development along the anterior-posterior axis
    • abnormal hair follicle structure (MGI Ref ID J:50050)
      • skin grafts of mutant skin transplanted onto nude mice exhibit giant disorganized hair-bud-like structures, some with hair-shaft-like material, in the vicinity of epidermis
      • absent hair follicles (MGI Ref ID J:50050)
        • by 18.5 dpc, homozygotes show a severe reduction in the number of induced hair follicles relative to wild-type mice
      • absent inner root sheath (MGI Ref ID J:50050)
        • mutant hair follicles fail to initiate development of the inner root sheath from the hair matrix (stages 3-5)
  • abnormal hair shaft morphology (MGI Ref ID J:50050)
    • skin grafts of mutant skin transplanted onto nude mice show abnormal ingrowth of the epidermis and consequently aberrant morphogenesis of the hair shaft
  • alopecia (MGI Ref ID J:50050)
    • skin grafts of mutant skin (epidermis and dermis) transplanted onto nude mice generate hairless, pigmented skin
    • some keratinized pigmented material resembling hair matrix is present, but no hair is formed
  • epidermal hyperplasia (MGI Ref ID J:50050)
    • skin grafts of mutant skin transplanted onto nude mice display hyperplasia and abnormal keratin expression in interfollicular epidermis
  • thickened epidermis (MGI Ref ID J:50050)
    • skin grafts of mutant skin transplanted onto nude mice exhibit a thickened epidermis with large disorganized ingrowths
  • digestive/alimentary phenotype
  • abnormal digestive system morphology (MGI Ref ID J:62158)
    • at 18.5 dpc, homozygotes display a smaller gastrointestinal tract relative to wild-type
    • abnormal anus morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, all homozygotes have an imperforate anus
    • abnormal colon morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, the mutant colon ends in a blind dilation that is not fused to the surface ectoderm; however, no aganglionic colon is observed
    • abnormal digestive organ placement (MGI Ref ID J:62158)
      • at 18.5 dpc, all homozygotes display an obvious malrotation of the gut, in the absence of reversions in gut situs
    • abnormal esophagus morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, the mutant esophagus tissue is reduced and fused to the trachea
      • tracheoesophageal fistula (MGI Ref ID J:50051)
        • at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
    • abnormal pancreas morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, 85% of homozygotes exhibit an annular pancreas
    • abnormal small intestine morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine; however, no intestinal dilation is observed
      • abnormal duodenum morphology (MGI Ref ID J:62158)
        • at 18.5 dpc, 67% of homozygotes display occlusion of the duodenum by overgrown villi, resembling duodenal stenosis
    • abnormal stomach morphology (MGI Ref ID J:62158)
      • at 18.5 dpc, all homozygotes exhibit intestinal transformation of the stomach epithelium
      • abnormal stomach glandular epithelium morphology (MGI Ref ID J:62158)
        • at 18.5 dpc, the mutant glandular epithelium displays histologic features that resemble intestinal metaplasia
      • stomach epithelial hyperplasia (MGI Ref ID J:62158)
        • at 18.5 dpc, all homozygotes display a significant overgrowth of stomach epithelium, in spite of normal rates of cell proliferation in the stomach
    • abnormal tracheal-esophageal septation (MGI Ref ID J:50051)
      • at 12.5 dpc, the trachea and esophagus of mutant mice remain fused at the tracheo-esophageal septum
  • respiratory system phenotype
  • abnormal lung development (MGI Ref ID J:50051)
    • although left and right buds form, mutant lungs fail to undergo lobation or subsequent extensive branching
    • impaired bronchiole branching (MGI Ref ID J:50051)
      • at 12.5 dpc, mutant lungs fail to branch or display one abnormally positioned branch point
      • in organ culture, mutant lungs fail to grow or branch extensively; bronchial mesenchyme cells detach from the endodermal epithelium
  • abnormal respiratory alveoli morphology (MGI Ref ID J:50051)
    • by 18.5 dpc, only a few primary branches and air sacs are present
  • abnormal tracheal cartilage morphology (MGI Ref ID J:50051)
    • in mutant trachea, cartilaginous rings are present but appear disorganized
  • abnormal tracheal smooth muscle morphology (MGI Ref ID J:50051)
    • in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent
  • abnormal tracheal-esophageal septation (MGI Ref ID J:50051)
    • at 12.5 dpc, the trachea and esophagus of mutant mice remain fused at the tracheo-esophageal septum
  • pulmonary hypoplasia (MGI Ref ID J:50051)
    • at 18.5 dpc, homozygotes display a rudimentary respiratory organ with a few large, poorly vascularized airways
  • tracheoesophageal fistula (MGI Ref ID J:50051)
    • at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
  • muscle phenotype
  • abnormal smooth muscle morphology (MGI Ref ID J:62158)
    • at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine
    • abnormal tracheal smooth muscle morphology (MGI Ref ID J:50051)
      • in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent
  • growth/size phenotype
  • reduced fetal size (MGI Ref ID J:62158)
    • at 18.5 dpc, mutant embryos have an overall reduced size relative to wild-type embryos
  • endocrine/exocrine gland phenotype
  • abnormal pancreas morphology (MGI Ref ID J:62158)
    • at 18.5 dpc, 85% of homozygotes exhibit an annular pancreas
  • nervous system phenotype
  • abnormal enteric neuron morphology (MGI Ref ID J:62158)
    • at 18.5 dpc, homozygotes show excessive and abnormally located neurons that differentiate under the epithelium and into the villi
  • skeleton phenotype
  • abnormal tracheal cartilage morphology (MGI Ref ID J:50051)
    • in mutant trachea, cartilaginous rings are present but appear disorganized

Shhtm1Amc/Shhtm1Amc

        involves: 129S1/Sv * 129X1/SvJ
  • embryogenesis phenotype
  • notochord degeneration (MGI Ref ID J:121553)
    • at E9.5
  • nervous system phenotype
  • holoprosencephaly (MGI Ref ID J:121553)
  • skeleton phenotype
  • abnormal vertebrae morphology (MGI Ref ID J:121553)
    • all ventral vertebral components are absent

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

Shhtm1Amc/Shhtm2Amc Tg(KRT14-cre)1Amc/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA   (conditional)
  • lethality-prenatal/perinatal
  • neonatal lethality (MGI Ref ID J:65294)
    • mutant newborns die within a day after birth
  • craniofacial phenotype
  • abnormal ameloblast morphology (MGI Ref ID J:65294)
    • at birth, functional odontoblast and ameloblast layers are present but display abnormal polarity and cellular architecture
    • 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
  • abnormal dentin morphology (MGI Ref ID J:65294)
    • 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
  • abnormal enamel morphology (MGI Ref ID J:65294)
    • 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
    • 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
  • abnormal incisor morphology (MGI Ref ID J:65294)
    • at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla
    • mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted
  • abnormal molar crown morphology (MGI Ref ID J:65294)
    • mandibular molars display a single irregular cusp; additional cusp formation is disrupted
  • abnormal skull morphology (MGI Ref ID J:65294)
    • at birth, mutant pups display flattened skulls
    • abnormal nasal bone morphology (MGI Ref ID J:65294)
      • at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
    • absent alveolar process (MGI Ref ID J:65294)
      • mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
  • arrest of tooth development (MGI Ref ID J:65294)
    • at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
    • growth retardation of incisors (MGI Ref ID J:65294)
      • at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
    • growth retardation of molars (MGI Ref ID J:65294)
      • at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
  • cleft palate (MGI Ref ID J:90909)
    • 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
  • small molars (MGI Ref ID J:65294)
    • at birth, mutant pups display small and abnormally shaped first molars in both the mandible and maxilla
    • maxillary molars are less affected than mandibular molars which are 25% of normal size
    • although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed
  • skeleton phenotype
  • *normal* skeleton phenotype (MGI Ref ID J:65294)
    • at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length
    • abnormal ameloblast morphology (MGI Ref ID J:65294)
      • at birth, functional odontoblast and ameloblast layers are present but display abnormal polarity and cellular architecture
      • 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
    • abnormal skull morphology (MGI Ref ID J:65294)
      • at birth, mutant pups display flattened skulls
      • abnormal nasal bone morphology (MGI Ref ID J:65294)
        • at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
      • absent alveolar process (MGI Ref ID J:65294)
        • mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
    • arrest of tooth development (MGI Ref ID J:65294)
      • at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
      • growth retardation of incisors (MGI Ref ID J:65294)
        • at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
      • growth retardation of molars (MGI Ref ID J:65294)
        • at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
  • vision/eye phenotype
  • eyelids open at birth (MGI Ref ID J:65294)
  • touch/vibrissae phenotype
  • absent vibrissae (MGI Ref ID J:65294)
  • respiratory system phenotype
  • abnormal breathing (MGI Ref ID J:65294)
    • at birth, mutant pups are observed gulping air
  • digestive/alimentary phenotype
  • cleft palate (MGI Ref ID J:90909)
    • 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart

Gene & Allele Details

Allele Symbol Shhtm1Amc
Allele Name targeted mutation 1, Andrew P McMahon
Common Name(s) Shh-; Shhn;
Mutation Made By Paula Lewis,   AstraZeneca, R&D Boston
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
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 A neomycin cassette replaced exon 2 and portions of the flanking intronic sequences. [MGI Ref ID J:50050]

Control Information

  Allele   Control
 Shhtm1Amc  Wild-type from the colony
 
  Considerations for Choosing Controls

Genotyping Protocols

Shhtm1Amc

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Shh
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
View Strains carrying other alleles of Shh     (4 strains)

Research Applications

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

Shhtm1Amc 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 Mortality
Skeletal Defects

Neurobiology Research
Neural Tube Defects
Neurodevelopmental Defects

Sensorineural Research
Eye Defects

References

Selected Reference(s)

St-Jacques B; Dassule HR; Karavanova I; Botchkarev VA; Li J; Danielian PS; McMahon JA; Lewis PM; Paus R; McMahon AP. 1998. Sonic hedgehog signaling is essential for hair development. Curr Biol 8(19):1058-68. [PubMed: 9768360]  [MGI Ref ID J:50050]

Additional References

Price and Supply Information

Strain Name: STOCK Shhtm1Amc/J
Stock Number: 003318

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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Control InformationView Control Information in Strain Details.

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Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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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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