About   Help   FAQ
Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Shhtm1Amc
targeted mutation 1, Andrew P McMahon
MGI:1934261
Summary 18 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Shhtm1Amc/Shhtm1Amc involves: 129/Sv * C57BL/6J * CBA/J MGI:3584154
hm2
Shhtm1Amc/Shhtm1Amc involves: 129S1/Sv * 129X1/SvJ MGI:3711886
hm3
Shhtm1Amc/Shhtm1Amc Not Specified MGI:2172132
hm4
Shhtm1Amc/Shhtm1Amc STOCK Shhtm1Amc/J MGI:3586338
ht5
Shhtm1Amc/Shhtm1.1Rseg involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 MGI:3851498
ht6
Shhtm1Amc/Shhtm2Amc involves: 129S1/Sv * 129X1/SvJ MGI:3584384
ht7
Shhtm1.1Dje/Shhtm1Amc involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N MGI:4948512
cn8
Gt(ROSA)26Sortm5(Etv4/en,-GFP)Amc/Gt(ROSA)26Sor+
Shhtm1Amc/Shhtm2Amc
Tg(Prrx1-cre)1Cjt/0
involves: 129 * C57BL/6 * CBA * SJL/J * Swiss Webster MGI:3848911
cn9
Disp1icb/Disp1icb
Shhtm1Amc/Shhtm5Amc
Tg(Sox2-cre)1Amc/0
involves: 129/Sv * C57BL/6J * SWR MGI:3513053
cn10
Shhtm1Amc/Shhtm2Amc
Tg(Thy1-cre)703Vaw/?
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 MGI:3759227
cn11
Shhtm1Amc/Shhtm2Amc
Tg(Hoxb7-cre)13Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:5441067
cn12
Shhtm1Amc/Shhtm2Amc
Tg(KRT14-cre)1Amc/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA MGI:3584381
cn13
Shhtm1Amc/Shhtm2Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0
involves: FVB/N MGI:3051584
cx14
Ihhtm1Amc/Ihhtm1Amc
Shhtm1Amc/Shhtm1Amc
involves: 129/Sv * C57BL/6J * CBA/J MGI:3584477
cx15
Disp1tm2.1Amc/Disp1tm2.1Amc
Shhtm1Amc/Shh+
involves: 129/Sv * C57BL/6J * SWR MGI:3513050
cx16
Nr5a1tm1.1Hain/Nr5a1tm1.1Hain
Shhtm1Amc/Shh+
involves: 129S1/Sv * 129X1/SvJ MGI:5292679
cx17
Disp1icb/Disp1tm1Amc
Shhtm1Amc/Shh+
involves: 129X1/SvJ * C57BL/6J MGI:3052728
cx18
Shhtm1Amc/Shhtm1Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-Shh)1Jaw/0
involves: FVB/N MGI:3051585


Genotype
MGI:3584154
hm1
Allelic
Composition
Shhtm1Amc/Shhtm1Amc
Genetic
Background
involves: 129/Sv * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• none of the homozygotes surviving to term live beyond this time
• only ~50% of homozygotes survive to term

digestive/alimentary system
• at 18.5 dpc, homozygotes display a smaller gastrointestinal tract relative to wild-type
• at 18.5 dpc, all homozygotes have an imperforate anus
• at 18.5 dpc, all homozygotes display an obvious malrotation of the gut, in the absence of reversions in gut situs
• at 18.5 dpc, the mutant esophagus tissue is reduced and fused to the trachea
• at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
• 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
• 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
• at 18.5 dpc, 67% of homozygotes display occlusion of the duodenum by overgrown villi, resembling duodenal stenosis
• at 18.5 dpc, the mutant glandular epithelium displays histologic features that resemble intestinal metaplasia
• at 18.5 dpc, all homozygotes display a significant overgrowth of stomach epithelium, in spite of normal rates of cell proliferation in the stomach
• at 18.5 dpc, all homozygotes exhibit intestinal transformation of the stomach epithelium

respiratory system
• poorly vascularized airways
• at 18.5 dpc, the mutant trachea and esophagus are fused to form a fistula-like fusion of the alimentary and respiratory tract
• in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent
• although left and right buds form, mutant lungs fail to undergo lobation or subsequent extensive branching
• 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
• by 18.5 dpc, only a few air sacs are present
• mutant lungs fail to undergo lobation
• at 18.5 dpc, homozygotes display a rudimentary respiratory organ with a few large, poorly vascularized airways
• in mutant trachea, cartilaginous rings are present but appear disorganized

muscle
• at 18.5 dpc, homozygotes show a 21% reduction in thickness of the circular smooth muscle layer along the small intestine
• in mutant trachea, the layer of smooth muscle that normally lines the proximal epithelium is absent

growth/size/body
• at 18.5 dpc, mutant embryos have an overall reduced size relative to wild-type embryos

endocrine/exocrine glands
• at 18.5 dpc, 85% of homozygotes exhibit an annular pancreas

nervous system
• at 18.5 dpc, homozygotes show excessive and abnormally located neurons that differentiate under the epithelium and into the villi

skeleton
• in mutant trachea, cartilaginous rings are present but appear disorganized

integument
• 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
• 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
• skin grafts of mutant skin transplanted onto nude mice show abnormal ingrowth of the epidermis and consequently aberrant morphogenesis of the hair shaft
• 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
• 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
• 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
• mutant hair follicles fail to initiate development of the inner root sheath from the hair matrix (stages 3-5)
• by 18.5 dpc, homozygotes show a severe reduction in the number of induced hair follicles relative to wild-type mice
• mutant hair buds fail to exhibit an obvious polarity; in contrast, wild-type follicles show a typical polarized development along the anterior-posterior axis
• skin grafts of mutant skin transplanted onto nude mice exhibit a reduced dermal fat layer
• mutant skin displays only a rudimentary dermal papilla, indicating abnormal epithelial-mesenchymal interactions
• skin grafts of mutant skin transplanted onto nude mice display hyperplasia and abnormal keratin expression in interfollicular epidermis
• skin grafts of mutant skin transplanted onto nude mice exhibit a thickened epidermis with large disorganized ingrowths

cardiovascular system
• poorly vascularized airways

cellular
• 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




Genotype
MGI:3711886
hm2
Allelic
Composition
Shhtm1Amc/Shhtm1Amc
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
embryo

nervous system

skeleton
• all ventral vertebral components are absent




Genotype
MGI:2172132
hm3
Allelic
Composition
Shhtm1Amc/Shhtm1Amc
Genetic
Background
Not Specified
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• homozygous mutants die shortly after birth

digestive/alimentary system
• 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
• reduced stomach size, particularly in the fore-stomach, at E12.5

respiratory system
• 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
• branching morphogenesis is impaired with the single tracheal-esophageal tube connected to the proximal and peripheral lung structures
• 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
• peripheral tubules are absent
• the pharynx is closed anteriorly
• the cartilaginous rings that normally surround the trachea are absent

skeleton
• the cartilaginous rings that normally surround the trachea are absent




Genotype
MGI:3586338
hm4
Allelic
Composition
Shhtm1Amc/Shhtm1Amc
Genetic
Background
STOCK Shhtm1Amc/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
digestive/alimentary system
• 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 glands
• 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




Genotype
MGI:3851498
ht5
Allelic
Composition
Shhtm1Amc/Shhtm1.1Rseg
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1.1Rseg mutation (1 available); any Shh mutation (26 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
embryo
N
• while organ size is reduced to various degrees, all organs are present and correctly localized unlike in Shh-null mice

growth/size/body
• body weight of mice is greatly reduced compared to controls

nervous system
• brain weight is less than controls
• olfactory bulb is disproportionately smaller than controls
• cerebella is 50% smaller than controls, which is disproportionately smaller compared to other organs

vision/eye
• eyes are small but are well-spaced unlike Shh-null mice that have improperly spaced eyes




Genotype
MGI:3584384
ht6
Allelic
Composition
Shhtm1Amc/Shhtm2Amc
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• compound heterozygotes for Shhtm1Amc and Shhtm2Amc are viable and fertile with no discernible phenotype




Genotype
MGI:4948512
ht7
Allelic
Composition
Shhtm1.1Dje/Shhtm1Amc
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1.1Dje mutation (0 available); any Shh mutation (26 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 80% of mice fail to gain weight and die by 7 days of age
• 20% survive to adulthood

growth/size/body
• normal weight at birth
• 80% fail to gain weight after birth and die by 7 days of age
• the 20% who survive remain remain small, 33% of normal weight

behavior/neurological
N
• normal suckling response
• dead pups often have milk in their stomach
• well coordinated motor control

homeostasis/metabolism
N
• normal blood glucose




Genotype
MGI:3848911
cn8
Allelic
Composition
Gt(ROSA)26Sortm5(Etv4/en,-GFP)Amc/Gt(ROSA)26Sor+
Shhtm1Amc/Shhtm2Amc
Tg(Prrx1-cre)1Cjt/0
Genetic
Background
involves: 129 * C57BL/6 * CBA * SJL/J * Swiss Webster
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm5(Etv4/en,-GFP)Amc mutation (0 available); any Gt(ROSA)26Sor mutation (310 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
Tg(Prrx1-cre)1Cjt mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
limbs/digits/tail
• at P1, digits appear posteriorized comparing relative digit length and phalanx morphology with that of controls Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice
• however, mice have the same number of digits as in Shhtm1Amc/Shhtm2Amc Tg(Prrx1-cre)1Cjt mice




Genotype
MGI:3513053
cn9
Allelic
Composition
Disp1icb/Disp1icb
Shhtm1Amc/Shhtm5Amc
Tg(Sox2-cre)1Amc/0
Genetic
Background
involves: 129/Sv * C57BL/6J * SWR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Disp1icb mutation (0 available); any Disp1 mutation (23 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm5Amc mutation (0 available); any Shh mutation (26 available)
Tg(Sox2-cre)1Amc mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• compound mutants die around birth unlike Disp1 single homozygotes which die before E9.5

craniofacial
• midline defects in the frontal nasal process are seen, however many of the developmental defects seen in Disp1 single homozygotes are rescued in the compound mutants




Genotype
MGI:3759227
cn10
Allelic
Composition
Shhtm1Amc/Shhtm2Amc
Tg(Thy1-cre)703Vaw/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
Tg(Thy1-cre)703Vaw mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

vision/eye
• glial progenitor cells are absent from the optic nerves
• optic nerves are thin, hypocellular and surrounded by a thick layer of pigmented cells that are continuous with the pigment epithelium but extend variable distances towards the ventral diencephalons
• optic nerves lack Ntn1- and Pax2-expressing astrocytes and are instead populated by pigment cells interspersed with retinal ganglion cell axons
• the distal two thirds of optic nerves lack Pax2-expressing glial cells
• while the optic cup and proximal optic stalk are normal initially, the optic primordial lags behind that in wild-type mice resulting in small eyes
• as early as E13 (J:83530)
• eyelids fail to close throughout gestation
• retinas are extensively disorganized
• the outer retinal layer contains many rosettes containing retinal progenitor cells and immature photoreceptors and, in some cases, cells extrude into the subretinal space
• lamination defects are observed at E17
• however, rosettes do not disrupt the retinal pigment epithelium
• retinal ganglion cell (RGC) axons exhibit guidance defects and are misrouted to the sub-retinal spaces in several regions of the retina and at the optic disc
• RGC axons that reach the optic disc never enter the optic nerve and instead remain coiled in the sub-retinal space
• however, dorsal ventral patterning and optic fissure closure are normal

nervous system
• mice exhibit mild to severe holoprosencephaly (J:78708)
• some mice exhibit holoprosencephaly (J:83530)
• however, development and expression of ventral markers in the hypothalamus are normal (J:83530)
• glial progenitor cells are absent from the optic nerves
• the distal two thirds of optic nerves lack Pax2-expressing glial cells
• retinal ganglion cell (RGC) axons exhibit guidance defects and are misrouted to the sub-retinal spaces in several regions of the retina and at the optic disc
• RGC axons that reach the optic disc never enter the optic nerve and instead remain coiled in the sub-retinal space
• however, dorsal ventral patterning and optic fissure closure are normal
• glial progenitor cells are absent from the optic nerves
• optic nerves are thin, hypocellular and surrounded by a thick layer of pigmented cells that are continuous with the pigment epithelium but extend variable distances towards the ventral diencephalons
• optic nerves lack Ntn1- and Pax2-expressing astrocytes and are instead populated by pigment cells interspersed with retinal ganglion cell axons
• the distal two thirds of optic nerves lack Pax2-expressing glial cells

craniofacial

growth/size/body
• as early as E13




Genotype
MGI:5441067
cn11
Allelic
Composition
Shhtm1Amc/Shhtm2Amc
Tg(Hoxb7-cre)13Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
Tg(Hoxb7-cre)13Amc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• 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
• however, no gross differences in glomerular size are observed
• newborn mice exhibit a 40% reduction in glomerular number
• at the newborn stage, cortical volume is reduced by 51%
• at 4 months of age, most of the inner medulla is lost in hydronephric kidneys
• at 4 months of age, most of the inner stripe of the outer medulla is lost in hydronephric kidneys
• at the newborn stage, medullary volume is reduced by 46%
• at 4 months of age, 50% of mice exhibit hydronephrosis
• however, no hydronephrosis is detected in newborn pups
• neonatal kidneys are 52% smaller than wild-type kidneys
• at E14.5, fewer mesenchymal cells line the ureteral epithelium relative to wild-type controls
• 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
• however, no differences in ureteral mesenchyme apoptosis are observed by TUNEL analysis
• a delay in smooth muscle differentiation is observed along the proximodistal axis of the ureter
• 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
• 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
• in addition, mesenchymal cells in the distal ureter are not as condensed as those in wild-type controls
• newborn mice exhibit prominent hydroureter, usually more severe in the proximal region
• at E14.5, ureter length is ~21% shorter than in wild-type controls




Genotype
MGI:3584381
cn12
Allelic
Composition
Shhtm1Amc/Shhtm2Amc
Tg(KRT14-cre)1Amc/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
Tg(KRT14-cre)1Amc mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutant newborns die within a day after birth

craniofacial
• at birth, mutant pups display flattened skulls
• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
• 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
• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
• 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
• 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
• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
• 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
• 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
• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
• the rudimentary palatal shelves are spaced widely apart
• the palatal shelves fail to develop beyond rudimentary processes

skeleton
N
• at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length
• at birth, mutant pups display flattened skulls
• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
• 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
• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
• 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
• 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
• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
• 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
• 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
• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced

vision/eye

respiratory system
• at birth, mutant pups are observed gulping air

digestive/alimentary system
• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
• the rudimentary palatal shelves are spaced widely apart
• the palatal shelves fail to develop beyond rudimentary processes

integument

growth/size/body
• 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
• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
• 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
• 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
• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
• 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
• 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
• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
• the rudimentary palatal shelves are spaced widely apart
• the palatal shelves fail to develop beyond rudimentary processes




Genotype
MGI:3051584
cn13
Allelic
Composition
Shhtm1Amc/Shhtm2Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0
Genetic
Background
involves: FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Shhtm2Amc mutation (1 available); any Shh mutation (26 available)
Tg(SFTPC-rtTA)5Jaw mutation (3 available)
Tg(tetO-cre)1Jaw mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants die shortly after birth when doxycycline is administered throughout gestation
• in the absence of doxycycline treatment mutants are viable

respiratory system
• lung and airway malformations are seen when doxycycline exposure occurs between E0.5 and E13.5
• doxycycline exposure after E13.5 does not result in any pulmonary or extrapulmonary abnormalities
• branching morphogenesis is abnormal with doxycycline treatment
• lungs are hypoplastic after doxycycline exposure
• peripheral tubule dilation is seen with doxycycline exposure
• cysts are seen in the peripheral lung tissue
• tracheal abnormalities are seen
• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
• fewer cartilaginous rings are seen with doxycycline treatment

skeleton
• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
• fewer cartilaginous rings are seen with doxycycline treatment




Genotype
MGI:3584477
cx14
Allelic
Composition
Ihhtm1Amc/Ihhtm1Amc
Shhtm1Amc/Shhtm1Amc
Genetic
Background
involves: 129/Sv * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ihhtm1Amc mutation (1 available); any Ihh mutation (5 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
embryo
• double homozygotes arrest at early somite stages




Genotype
MGI:3513050
cx15
Allelic
Composition
Disp1tm2.1Amc/Disp1tm2.1Amc
Shhtm1Amc/Shh+
Genetic
Background
involves: 129/Sv * C57BL/6J * SWR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Disp1tm2.1Amc mutation (0 available); any Disp1 mutation (23 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• the reduction of pMN and pV2 progenitors results in a decrease in motorneuron precursors that are also abnormally positioned at the ventral midline
• the floor plate is absent and the ventral midline has reduced numbers of the ventral most neural progenitors

embryo
• the floor plate is absent and the ventral midline has reduced numbers of the ventral most neural progenitors

cellular
• the reduction of pMN and pV2 progenitors results in a decrease in motorneuron precursors that are also abnormally positioned at the ventral midline




Genotype
MGI:5292679
cx16
Allelic
Composition
Nr5a1tm1.1Hain/Nr5a1tm1.1Hain
Shhtm1Amc/Shh+
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr5a1tm1.1Hain mutation (0 available); any Nr5a1 mutation (16 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• decreased adrenal aldosterone levels
• decrease is less severe than in mice homozygous for Nr5a1tm1.1Hain alone




Genotype
MGI:3052728
cx17
Allelic
Composition
Disp1icb/Disp1tm1Amc
Shhtm1Amc/Shh+
Genetic
Background
involves: 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Disp1icb mutation (0 available); any Disp1 mutation (23 available)
Disp1tm1Amc mutation (0 available); any Disp1 mutation (23 available)
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• no heart looping but normal embryo turning

nervous system
• ventral midline of neural tube occupied by a reduced population of motor neuron progenitors

craniofacial
• extreme proboscis-like nasal process

growth/size/body
• extreme proboscis-like nasal process

Mouse Models of Human Disease
OMIM ID Ref(s)
Holoprosencephaly 3; HPE3 142945 J:92058




Genotype
MGI:3051585
cx18
Allelic
Composition
Shhtm1Amc/Shhtm1Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-Shh)1Jaw/0
Genetic
Background
involves: FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Shhtm1Amc mutation (1 available); any Shh mutation (26 available)
Tg(SFTPC-rtTA)5Jaw mutation (3 available)
Tg(tetO-Shh)1Jaw mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants die shortly after birth even when doxycycline is administered throughout gestation

respiratory system
• a significant increase in peripheral lung tissue and relatively normal branching morphogenesis are seen with doxycycline treatment; however, lobulation of the lungs is not restored
• doxycycline treatment does not restore tracheal-bronchial cartilaginous ring formation

skeleton
• doxycycline treatment does not restore tracheal-bronchial cartilaginous ring formation





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources
Funding Information
Warranty Disclaimer & Copyright Notice
Send questions and comments to User Support.
last database update
05/17/2016
MGI 6.03
The Jackson Laboratory