JAX
Mouse Strain Datasheet - 003318
STOCK Shhtm1Amc/J
Also Known As: Shh-
These Shh knock-out mice exhibit defects in the establishment and maintenance of midline structures.
Donating Investigator
Andrew P McMahon, University of Southern California
Genetic overview
| Genetic Background | Generation |
|---|---|
|
|
Shhtm1Amc
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Shh | sonic hedgehog |
Research Applications
- Cancer Research
- Cell Biology Research
- Dermatology Research
- Developmental Biology Research
- Neurobiology Research
- Sensorineural Research
Detailed 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 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.
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 mesonephric duct and its developmental derivatives (Stock No. 004692), this mutant mouse strain may be useful in studies of hedgehog signaling and cell proliferation/differentiation in mesenchymal cells of the kidney.
Control Suggestions
Selected References
- 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: 9768360MGI: J:50050
Shhtm1Amc
Allele Symbol: Shhtm1Amc
| Allele Name | targeted mutation 1, Andrew P McMahon |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | Shh-; Shhn |
| 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 |
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> |
| Chromosome | 5 |
| Molecular Note | A neomycin cassette replaced exon 2 and portions of the flanking intronic sequences. |
| Mutations Made By | Dr. Paula Lewis, AstraZeneca, R&D Boston |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: 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 Lethality
- Skeletal Defects
- Neurobiology Research
- Neural Tube Defects
- Neurodevelopmental Defects
- Sensorineural Research
- Eye Defects
Mammalian Phenotype Terms by Genotype
Genotype: Shhtm1Amc/Shhtm1Amc
STOCK Shhtm1Amc/J
digestive/alimentary phenotype
- abnormal submandibular gland morphology
- 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 (MGI Ref ID J:89200)
- at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG) (MGI Ref ID J:89200)
- 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) (MGI Ref ID J:89200)
- 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 (MGI Ref ID J:89200)
endocrine/exocrine gland phenotype
- abnormal submandibular gland morphology
- 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 (MGI Ref ID J:89200)
- at E13.5 and E15.5, homozygotes show a severely reduced, dysplastic remnant of the submandibular salivary gland (SMG) (MGI Ref ID J:89200)
- 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) (MGI Ref ID J:89200)
- 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 (MGI Ref ID J:89200)
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Shhtm1Amc/Shhtm1Amc
Not Specified
mortality/aging
- neonatal lethality, complete penetrance
- homozygous mutants die shortly after birth (MGI Ref ID J:91723)
digestive/alimentary phenotype
- small stomach
- reduced stomach size, particularly in the fore-stomach, at E12.5 (MGI Ref ID J:98520)
- tracheoesophageal fistula
respiratory system phenotype
- abnormal branching involved in lung morphogenesis
- branching morphogenesis is impaired with the single tracheal-esophageal tube connected to the proximal and peripheral lung structures (MGI Ref ID J:91723)
- abnormal bronchus morphology
- peripheral tubules are absent (MGI Ref ID J:91723)
- abnormal pharynx morphology
- the pharynx is closed anteriorly (MGI Ref ID J:91723)
- absent tracheal cartilage rings
- the cartilaginous rings that normally surround the trachea are absent (MGI Ref ID J:91723)
- pulmonary hypoplasia
- tracheoesophageal fistula
skeleton phenotype
- absent tracheal cartilage rings
- the cartilaginous rings that normally surround the trachea are absent (MGI Ref ID J:91723)
Genotype: Shhtm1Amc/Shhtm1Amc
involves: 129S1/Sv * 129X1/SvJ
embryo phenotype
- notochord degeneration
- at E9.5 (MGI Ref ID J:121553)
nervous system phenotype
- holoprosencephaly
- (MGI Ref ID J:121553)
skeleton phenotype
- abnormal vertebrae morphology
- all ventral vertebral components are absent (MGI Ref ID J:121553)
Genotype: Shhtm1Amc/Shhtm1Amc
involves: 129/Sv * C57BL/6J * CBA/J
mortality/aging
- perinatal lethality, complete penetrance
- none of the homozygotes surviving to term live beyond this time (MGI Ref ID J:50050)
- prenatal lethality, incomplete penetrance
- only ~50% of homozygotes survive to term (MGI Ref ID J:50050)
cardiovascular system phenotype
- abnormal lung vasculature morphology
- poorly vascularized airways (MGI Ref ID J:50051)
cellular phenotype
- decreased keratinocyte proliferation
- at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type, with no difference observed in apoptosis (MGI Ref ID J:50051)
digestive/alimentary phenotype
- abnormal colon morphology
- 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 (MGI Ref ID J:62158)
- abnormal digestive organ placement
- at 18.5 dpc, all homozygotes display an obvious malrotation of the gut, in the absence of reversions in gut situs (MGI Ref ID J:62158)
- abnormal digestive system morphology
- at 18.5 dpc, homozygotes display a smaller gastrointestinal tract relative to wild-type (MGI Ref ID J:62158)
- abnormal duodenum morphology
- at 18.5 dpc, 67% of homozygotes display occlusion of the duodenum by overgrown villi, resembling duodenal stenosis (MGI Ref ID J:62158)
- abnormal esophagus morphology
- at 18.5 dpc, the mutant esophagus tissue is reduced and fused to the trachea (MGI Ref ID J:62158)
- abnormal small intestine morphology
- 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 (MGI Ref ID J:62158)
- abnormal stomach glandular epithelium morphology
- at 18.5 dpc, the mutant glandular epithelium displays histologic features that resemble intestinal metaplasia (MGI Ref ID J:62158)
- anal atresia
- at 18.5 dpc, all homozygotes have an imperforate anus (MGI Ref ID J:62158)
- gastric metaplasia
- at 18.5 dpc, all homozygotes exhibit intestinal transformation of the stomach epithelium (MGI Ref ID J:62158)
- stomach epithelial hyperplasia
- at 18.5 dpc, all homozygotes display a significant overgrowth of stomach epithelium, in spite of normal rates of cell proliferation in the stomach (MGI Ref ID J:62158)
- tracheoesophageal fistula
- at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract (MGI Ref ID J:50051)
respiratory system phenotype
- abnormal lung development
- although left and right buds form, mutant lungs fail to undergo lobation or subsequent extensive branching (MGI Ref ID J:50051)
- abnormal lung saccule morphology
- by 18.5 dpc, only a few air sacs are present (MGI Ref ID J:50051)
- abnormal lung vasculature morphology
- poorly vascularized airways (MGI Ref ID J:50051)
- abnormal tracheal cartilage morphology
- in mutant trachea, cartilaginous rings are present but appear disorganized (MGI Ref ID J:50051)
- abnormal tracheal smooth muscle morphology
- in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent (MGI Ref ID J:50051)
- impaired branching involved in bronchus morphogenesis
- impaired lung lobe morphogenesis
- mutant lungs fail to undergo lobation (MGI Ref ID J:50051)
- pulmonary hypoplasia
- at 18.5 dpc, homozygotes display a rudimentary respiratory organ with a few large, poorly vascularized airways (MGI Ref ID J:50051)
- tracheoesophageal fistula
- at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract (MGI Ref ID J:50051)
muscle phenotype
- abnormal smooth muscle morphology
- at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine (MGI Ref ID J:62158)
- abnormal tracheal smooth muscle morphology
- in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent (MGI Ref ID J:50051)
growth/size/body region phenotype
- decreased fetal size
- at 18.5 dpc, mutant embryos have an overall reduced size relative to wild-type embryos (MGI Ref ID J:62158)
endocrine/exocrine gland phenotype
- annular pancreas
- at 18.5 dpc, 85% of homozygotes exhibit an annular pancreas (MGI Ref ID J:62158)
nervous system phenotype
- abnormal enteric neuron morphology
- at 18.5 dpc, homozygotes show excessive and abnormally located neurons that differentiate under the epithelium and into the villi (MGI Ref ID J:62158)
skeleton phenotype
- abnormal tracheal cartilage morphology
- in mutant trachea, cartilaginous rings are present but appear disorganized (MGI Ref ID J:50051)
integument phenotype
- abnormal dermal layer morphology
- skin grafts of mutant skin transplanted onto nude mice exhibit a reduced dermal fat layer (MGI Ref ID J:50050)
- abnormal dermis papillary layer morphology
- mutant skin displays only a rudimentary dermal papilla, indicating abnormal epithelial-mesenchymal interactions (MGI Ref ID J:50050)
- abnormal hair follicle development
- 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 (MGI Ref ID J:50050)
- homozygotes display delayed hair folliculoenesis: embryonic follicles are arrested shortly after induction and fail to progress beyond stage 2 (MGI Ref ID J:50050)
- abnormal hair follicle morphology
- 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 (MGI Ref ID J:50050)
- at 15.5 dpc, wild-type hair follicles have progressed to stage 2, whereas mutant follicles at still at stage 1 or 0 (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 (MGI Ref ID J:50050)
- abnormal hair follicle orientation
- mutant hair buds fail to exhibit an obvious polarity; in contrast, wild-type follicles show a typical polarized development along the anterior-posterior axis (MGI Ref ID J:50050)
- abnormal hair shaft morphology
- skin grafts of mutant skin transplanted onto nude mice show abnormal ingrowth of the epidermis and consequently aberrant morphogenesis of the hair shaft (MGI Ref ID J:50050)
- absent hair follicle inner root sheath
- mutant hair follicles fail to initiate development of the inner root sheath from the hair matrix (stages 3-5) (MGI Ref ID J:50050)
- absent hair follicles
- by 18.5 dpc, homozygotes show a severe reduction in the number of induced hair follicles relative to wild-type mice (MGI Ref ID J:50050)
- alopecia
- decreased keratinocyte proliferation
- at 18.5 dpc, mutant hair follicles at stage 1-2 show a 40% decline in keratinocyte proliferation relative to wild-type, with no difference observed in apoptosis (MGI Ref ID J:50051)
- epidermal hyperplasia
- skin grafts of mutant skin transplanted onto nude mice display hyperplasia and abnormal keratin expression in interfollicular epidermis (MGI Ref ID J:50050)
- thick epidermis
- skin grafts of mutant skin transplanted onto nude mice exhibit a thickened epidermis with large disorganized ingrowths (MGI Ref ID J:50050)
The following phenotype relates to a compound genotype created using this strain
Genotype: Shhtm1Amc/Shhtm2Amc Tg(Hoxb7-cre)13Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
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
- 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)
- decreased renal glomerulus number
- newborn mice exhibit a 40% reduction in glomerular number (MGI Ref ID J:79481)
- hydronephrosis
- 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)
- renal hypoplasia
- (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)
Genotype: Shhtm1Amc/Shhtm2Amc Tg(KRT14-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
mortality/aging
- neonatal lethality, complete penetrance
- 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 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
- abnormal molar crown morphology
- mandibular molars display a single irregular cusp; additional cusp formation is disrupted (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)
- abnormal palatal shelf fusion at midline
- the rudimentary palatal shelves are spaced widely apart (MGI Ref ID J:90909)
- absent alveolar process
- mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent (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)
- 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)
- palatal shelf hypoplasia
- the palatal shelves fail to develop beyond rudimentary processes (MGI Ref ID J:90909)
- small molars
- although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed (MGI Ref ID J:65294)
- 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)
skeleton 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 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
- abnormal molar crown morphology
- mandibular molars display a single irregular cusp; additional cusp formation is disrupted (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)
- 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)
- 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)
- skeleton phenotype
- at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length (MGI Ref ID J:65294)
- small molars
- although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed (MGI Ref ID J:65294)
- 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)
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
- abnormal palatal shelf fusion at midline
- the rudimentary palatal shelves are spaced widely apart (MGI Ref ID J:90909)
- cleft secondary palate
- 85% exhibit a cleft palate with rudimentary palatal shelves 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)
growth/size/body region 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 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
- abnormal molar crown morphology
- mandibular molars display a single irregular cusp; additional cusp formation is disrupted (MGI Ref ID J:65294)
- abnormal palatal shelf fusion at midline
- the rudimentary palatal shelves are spaced widely apart (MGI Ref ID J:90909)
- 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)
- 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)
- palatal shelf hypoplasia
- the palatal shelves fail to develop beyond rudimentary processes (MGI Ref ID J:90909)
- small molars
- although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed (MGI Ref ID J:65294)
- 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)
References
- 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: 9768360MGI: J:50050
Additional References
- Chiang C; Litingtung Y; Lee E; Young KE; Corden JL; Westphal H; Beachy PA. 1996. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383(6599):407-13. PubMed: 8837770MGI: J:35802
- Fedtsova N; Perris R; Turner EE. 2003. Sonic hedgehog regulates the position of the trigeminal ganglia. Dev Biol 261(2):456-69. PubMed: 14499653MGI: J:85580
- Jaskoll T; Leo T; Witcher D; Ormestad M; Astorga J; Bringas P Jr; Carlsson P; Melnick M. 2004. Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis. Dev Dyn 229(4):722-32. PubMed: 15042696MGI: J:89200
Additional - Shhtm1Amc 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: 20724449MGI: J:168361
- Allen BL; Song JY; Izzi L; Althaus IW; Kang JS; Charron F; Krauss RS; McMahon AP. 2011. Overlapping Roles and Collective Requirement for the Coreceptors GAS1, CDO, and BOC in SHH Pathway Function. Dev Cell 20(6):775-87. PubMed: 21664576MGI: J:173604
- Allen BL; Tenzen T; McMahon AP. 2007. The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev 21(10):1244-57. PubMed: 17504941MGI: J:121553
- Aoto K; Shikata Y; Imai H; Matsumaru D; Tokunaga T; Shioda S; Yamada G; Motoyama J. 2009. Mouse Shh is required for prechordal plate maintenance during brain and craniofacial morphogenesis. Dev Biol 327(1):106-20. PubMed: 19103193MGI: J:145732
- 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: 22745311MGI: J:185651
- Bok J; Dolson DK; Hill P; Ruther U; Epstein DJ; Wu DK. 2007. Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear. Development 134(9):1713-22. PubMed: 17395647MGI: J:121232
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