Analysis Tools
normal phenotype
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• compound heterozygotes for Shhtm1Amc and Shhtm2Amc are viable and fertile with no discernible phenotype
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Allele Symbol Allele Name Allele ID |
Shhtm2Amc targeted mutation 2, Andrew P McMahon MGI:1934268 |
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| Summary |
16 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• compound heterozygotes for Shhtm1Amc and Shhtm2Amc are viable and fertile with no discernible phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• ventral neural tube patterning defects are seen
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• ventral neural tube patterning defects are seen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E10.5 and E18.5, mice exhibit abnormal arch-artery patterning compared to in wild-type mice
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• at E10.5, mice exhibit short outflow tract compared with wild-type mice
• mice exhibit cell death in the anterior heart field unlike in wild-type mice
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• at E18.5
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• mice exhibit cell death in neural crest cells unlike in wild-type mice
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• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice
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• mice exhibit cell death in neural crest cells unlike in wild-type mice
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• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal medial motor column (MMC) and hypaxial motor column (HMC) development at age E12.5
• normal proliferation of neural stem cells and overall spinal cord dorsal-ventral patterning at age E12.5
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• at age E12.5
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• ~30% decrease in LMCm (medial) and LMCl (lateral) neurons at age E12.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice survive only until 4-6 weeks of age
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• pups display movement disorders characteristic of abnormal cerebellar function
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• cerebellar development is more severely affected than in Shhtm2Amc/Shhtm3Amc;Tg(Pcp2-cre)1Amc mice
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• external germinal layer (EGL) is thin at E18.5
• at P5 there is no EGL
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• at P5 cells form a broad densely packed layer at P5; dendrite projections of Purkinje cells are hard to distinguish
• at P14 there is a mixture of Purkinje cell bodies and disorganized cellular projections
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• decreased by 25% at E18.5
• at P5 cell number is reduced by 50%
• in adults, number is reduced by 65%
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• there is no apparent inner germinal layer (IGL) at P5, although at P5 some scattered granule cells can be seen
• in the adult cerebellum, there is no IGL
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• proliferation of granule neuron progenitors is absent in the EGL at E18.5 and P5
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• in the adult cerebellum, molecular layer is absent
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• at E18.5 pups have no lobules
• in the adult cerebellum, there is a loss of rostral lobes
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• at P5, cerebellum is small with some rudimentary lobules
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• disorganization of Bergmann glia is more severe than in Shhtm2Amc/Shhtm3Amc;Tg(Pcp2-cre)1Amc mice post P5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• pups display movement disorders characteristic of abnormal cerebellar function
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• at E18.5, cerebellum is detected to be abnormal with immature fissures and a reduction in the external granule layer; however no difference in cerebellar volume is evident between mutants and wild-type
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• at E18.5 mutants have 5 rudimentary lobules
• at P5, cerebellum has small primitive lobules
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• at P5 cells are dispersed in a thinner layer than in control Shhtm2Amc/Shhtm3Amc control mice or Shhtm2Amc/Shhtm3Amc;Tg(Pax2-cre)1Amc mice
• dendrite projections of cells are hard to distinguish
• at P14, there is a layer of Purkinje neurons that is better organized than in Shhtm2Amc/Shhtm3Amc;Tg(Pax2-cre)1Amc mice
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• at P5 number is reduced by 20% compared to controls
• in adults, a 35% reduction is apparent
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• in adults, cerebellum is small but has distinct lobes with Purkinje cells organized into a 1-2 cell layer overlayed by a thin inner germinal layer
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die at birth
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• 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
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• 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
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• as early as E13
(J:83530)
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• eyelids fail to close throughout gestation
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• 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
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• 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
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• 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)
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• glial progenitor cells are absent from the optic nerves
• the distal two thirds of optic nerves lack Pax2-expressing glial cells
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• 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
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• 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
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• as early as E13
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• newborn mice exhibit a 40% reduction in glomerular number
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• at the newborn stage, cortical volume is reduced by 51%
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• at 4 months of age, most of the inner medulla is lost in hydronephric kidneys
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• at 4 months of age, most of the inner stripe of the outer medulla is lost in hydronephric kidneys
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• at the newborn stage, medullary volume is reduced by 46%
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• at 4 months of age, 50% of mice exhibit hydronephrosis
• however, no hydronephrosis is detected in newborn pups
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• neonatal kidneys are 52% smaller than wild-type kidneys
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• 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
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• 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
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• newborn mice exhibit prominent hydroureter, usually more severe in the proximal region
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• at E14.5, ureter length is ~21% shorter than in wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• total parietal cell number remains unchanged following tamoxifen treatment
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• at 7 and 60 days after final tamoxifen injection, expansion of surface mucous cells (foveolar hyperplasia) is observed, but at 150 days, surface mucous cell numbers are comparable to controls
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• parietal cells do not function in mutants treated with tamoxifen; parietal cells do not secrete acid in response to histamine stimulation
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• in an acetic acid ulceration model, healing is delayed relative to controls at 7 days after ulcer induction (ulcer size is decreased in controls); granulation tissue below the ulcer is observed in controls but not in mutants 7 days after induction
• in contrast to control mice, mutants do not exhibit macrophage recruitment to the ulcer site 2 days after ulcer induction; macrophage numbers are increased in stomachs of injured controls, but not in mutants
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• 7 days after acetic acid injury, control mice display an increase in new microvessels compared to PBS-treated controls, but PBS-treated mutants have significantly fewer CD31-positive microvessels relative to controls with no significant change after acetic acid injury
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant newborns die within a day after birth
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• at birth, mutant pups display flattened skulls
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• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
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• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla
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• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted
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• at birth, incisors are only 5% of normal size
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• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
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• 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
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• the dental cord is absent in mandibular molars
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• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
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• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
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• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
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• 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
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• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture
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• 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
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• at birth, functional 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
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• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
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• the rudimentary palatal shelves are spaced widely apart
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• the palatal shelves fail to develop beyond rudimentary processes
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• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
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| N |
• at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length
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• at birth, mutant pups display flattened skulls
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• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
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• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla
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• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted
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• at birth, incisors are only 5% of normal size
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• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
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• 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
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• the dental cord is absent in mandibular molars
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• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
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• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
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• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
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• 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
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• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture
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• 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
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• at birth, functional 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
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• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
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• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
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• the rudimentary palatal shelves are spaced widely apart
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• the palatal shelves fail to develop beyond rudimentary processes
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• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
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• at birth, mutant pups are observed gulping air
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• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent
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• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla
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• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted
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• at birth, incisors are only 5% of normal size
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• mandibular molars display a single irregular cusp; additional cusp formation is disrupted
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• 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
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• the dental cord is absent in mandibular molars
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• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology
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• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars
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• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors
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• 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
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• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture
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• 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
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• at birth, functional 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
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• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced
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• the rudimentary palatal shelves are spaced widely apart
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• the palatal shelves fail to develop beyond rudimentary processes
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• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• adrenal glands exhibit a decrease in stem/precursor cells compared with wild-type mice
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• the number of adrenocortical cells is decreased while their size is increased compared to in wild-type mice
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• at P5
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• at E16.5 and P5, adrenal gland cells exhibit reduced proliferation compared with wild-type cells
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• at P21
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• death by P15
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• animals are smaller than littermates, but are postnatally viable and have relatively normal gross morphology
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• marked reduction in growth by the second postnatal week
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• pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week
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• reductions of somatostatin- and parvalbumin-expressing interneurons in somatosensory cortex
• somatostatin- and Npy-expressing interneurons are also reduced in the striatum
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• 10% decrease in cortical thickness at P12
(J:102950)
• animals display slightly smaller brain size than control littermates, but overall morphology of brain is relatively normal
(J:147427)
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• thalamus organization is disrupted in mutants based on molecular marker analysis
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• reduced interneuron fate determining gene Nkx2.1 expression in progenitors of the medial ganglionic eminence (MGE) cells in S-phase
• a subtle disruption of MGE patterning indicated by reduction of Gli1 and Nkx6.2 expression is observed
• however, other aspects of MGE progenitor identity are maintained
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• pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants die shortly after birth when doxycycline is administered throughout gestation
• in the absence of doxycycline mutants are viable
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• 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
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• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue
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• branching morphogenesis is abnormal
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• lungs are hypoplastic when doxycycline is administered throughout gestation
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• peripheral tubule dilation is seen after doxycycline exposure
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• tracheal abnormalities are seen
• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities
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• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
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• fewer cartilaginous rings are seen after doxycycline exposure
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• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
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• fewer cartilaginous rings are seen after doxycycline exposure
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• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants die shortly after birth when doxycycline is administered throughout gestation
• in the absence of doxycycline treatment mutants are viable
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• 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
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• branching morphogenesis is abnormal with doxycycline treatment
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• lungs are hypoplastic after doxycycline exposure
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• peripheral tubule dilation is seen with doxycycline exposure
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• tracheal abnormalities are seen
• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities
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• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
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• fewer cartilaginous rings are seen with doxycycline treatment
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• the cartilaginous rings that normal surround the trachea are malformed with incomplete rings found along the ventral midline after doxycycline exposure
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• fewer cartilaginous rings are seen with doxycycline treatment
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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