Phenotypes associated with this allele

• Allele Symbol: Shh^tm2Amc
• Allele Name: targeted mutation 2, Andrew P McMahon
• Allele ID: MGI:1934268
• Summary: 16 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Shh^tm1Amc/Shh^tm2Amc	involves: 129S1/Sv * 129X1/SvJ	MGI:3584384
cn2	Shh^tm1(EGFP/cre)Cjt/Shh^tm2Amc	involves: 129/Sv * C57BL/6J * SWR	MGI:3513051
cn3	Gt(ROSA)26Sor^tm5(Etv4/en,-GFP)Amc/Gt(ROSA)26Sor^+ Shh^tm1Amc/Shh^tm2Amc Tg(Prrx1-cre)1Cjt/0	involves: 129 * C57BL/6 * CBA * SJL/J * Swiss Webster	MGI:3848911
cn4	Shh^tm1Chg/Shh^tm2Amc Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:4843919
cn5	Olig2^tm1(cre)Tmj/Olig2^+ Shh^tm2Amc/Shh^tm2Amc	involves: 129S1/Sv * 129X1/SvJ	MGI:6357927
cn6	Shh^tm2Amc/Shh^tm3Amc Tg(Pax2-cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:3656220
cn7	Shh^tm2Amc/Shh^tm3Amc Tg(Pcp2-cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * Black Swiss	MGI:3656218
cn8	Shh^tm1Amc/Shh^tm2Amc Tg(Thy1-cre)703Vaw/?	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6	MGI:3759227
cn9	Shh^tm1Amc/Shh^tm2Amc Tg(Hoxb7-cre)13Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5441067
cn10	Shh^tm2Amc/Shh^tm2Amc Tg(Atp4b-cre/ERT2)1Jrgo/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5496012
cn11	Shh^tm1Amc/Shh^tm2Amc Tg(KRT14-cre)1Amc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3584381
cn12	Shh^tm2Amc/Shh^tm2.1Amc Tg(Nr5a1-cre)2Klp/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N	MGI:4889096
cn13	Gata6^tm2.1Sad/Gata6^tm2.1Sad Shh^tm2Amc/Shh^tm2Amc Tg(Prrx1-cre)1Cjt/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J	MGI:5550094
cn14	Shh^tm2Amc/Shh^tm2Amc Tg(Nes-cre)1Kln/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3617985
cn15	Shh^tm2Amc/Shh^tm2Amc Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: FVB/N	MGI:3051583
cn16	Shh^tm1Amc/Shh^tm2Amc Tg(SFTPC-rtTA)5Jaw/0 Tg(tetO-cre)1Jaw/0	involves: FVB/N	MGI:3051584

Genotype
MGI:3584384

ht1

• Allelic Composition: Shh^tm1Amc/Shh^tm2Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

normal phenotype

no abnormal phenotype detected ( J:65294 )

• compound heterozygotes for Shh^tm1Amc and Shh^tm2Amc are viable and fertile with no discernible phenotype

Genotype
MGI:3513051

cn2

• Allelic Composition: Shh^{tm1(EGFP/cre)Cjt}/Shh^tm2Amc
• Genetic Background: involves: 129/Sv * C57BL/6J * SWR

vision/eye

cyclopia ( J:94270 )

• homozygous mutants have a cyclopic head similar to Shh null mutants

nervous system

abnormal neural tube morphology ( J:94270 )

• ventral neural tube patterning defects are seen

embryo

abnormal neural tube morphology ( J:94270 )

• ventral neural tube patterning defects are seen

Genotype
MGI:3848911

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm5(Etv4/en,-GFP)Amc}/Gt(ROSA)26Sor⁺; Shh^tm1Amc/Shh^tm2Amc; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129 * C57BL/6 * CBA * SJL/J * Swiss Webster

limbs/digits/tail

abnormal digit morphology ( J:149478 )

• at P1, digits appear posteriorized comparing relative digit length and phalanx morphology with that of controls Shh^tm1Amc/Shh^tm2Amc Tg(Prrx1-cre)1Cjt mice

• however, mice have the same number of digits as in Shh^tm1Amc/Shh^tm2Amc Tg(Prrx1-cre)1Cjt mice

Genotype
MGI:4843919

cn4

• Allelic Composition: Shh^tm1Chg/Shh^tm2Amc; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

abnormal artery morphology ( J:135134 )

• at E10.5 and E18.5, mice exhibit abnormal arch-artery patterning compared to in wild-type mice

abnormal cardiac outflow tract development ( J:135134 )

• 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

persistent truncus arteriosus ( J:135134 )

• at E18.5

embryo

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

cellular

abnormal neural crest cell apoptosis ( J:135134 )

• mice exhibit cell death in neural crest cells unlike in wild-type mice

abnormal neural crest cell migration ( J:135134 )

• mice exhibit abnormal neural crest cells localization and septation defects compared with wild-type mice

Genotype
MGI:6357927

cn5

• Allelic Composition: Olig2^tm1(cre)Tmj/Olig2⁺; Shh^tm2Amc/Shh^tm2Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

nervous system phenotype ( J:277700 )

N • normal medial motor column (MMC) and hypaxial motor column (HMC) development at age E12.5

N • normal proliferation of neural stem cells and overall spinal cord dorsal-ventral patterning at age E12.5

decreased motor neuron number ( J:277700 )

• at age E12.5

abnormal spinal cord lateral motor column morphology ( J:277700 )

• ~30% decrease in LMCm (medial) and LMCl (lateral) neurons at age E12.5

Genotype
MGI:3656220

cn6

• Allelic Composition: Shh^tm2Amc/Shh^tm3Amc; Tg(Pax2-cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss

mortality/aging

premature death ( J:92189 )

• mice survive only until 4-6 weeks of age

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:92189 )

• pups display movement disorders characteristic of abnormal cerebellar function

ataxia ( J:92189 )

nervous system

abnormal cerebellum morphology ( J:92189 )

abnormal cerebellum development ( J:92189 )

• cerebellar development is more severely affected than in Shh^tm2Amc/Shh^tm3Amc;Tg(Pcp2-cre)1Amc mice

abnormal cerebellum external granule cell layer morphology ( J:92189 )

• external germinal layer (EGL) is thin at E18.5

• at P5 there is no EGL

abnormal cerebellar Purkinje cell layer ( J:92189 )

• 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

decreased Purkinje cell number ( J:92189 )

• decreased by 25% at E18.5

• at P5 cell number is reduced by 50%

• in adults, number is reduced by 65%

abnormal cerebellar granule layer morphology ( J:92189 )

• 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

abnormal cerebellar granule cell morphology ( J:92189 )

• proliferation of granule neuron progenitors is absent in the EGL at E18.5 and P5

abnormal cerebellar molecular layer ( J:92189 )

• in the adult cerebellum, molecular layer is absent

absent cerebellar lobules ( J:92189 )

• at E18.5 pups have no lobules

• in the adult cerebellum, there is a loss of rostral lobes

small cerebellum ( J:92189 )

• at P5, cerebellum is small with some rudimentary lobules

abnormal astrocyte morphology ( J:92189 )

• disorganization of Bergmann glia is more severe than in Shh^tm2Amc/Shh^tm3Amc;Tg(Pcp2-cre)1Amc mice post P5

Genotype
MGI:3656218

cn7

• Allelic Composition: Shh^tm2Amc/Shh^tm3Amc; Tg(Pcp2-cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:92189 )

• pups display movement disorders characteristic of abnormal cerebellar function

ataxia ( J:92189 )

nervous system

abnormal cerebellum morphology ( J:92189 )

• 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

abnormal cerebellum development ( J:92189 )

abnormal cerebellar lobule formation ( J:92189 )

• at E18.5 mutants have 5 rudimentary lobules

• at P5, cerebellum has small primitive lobules

thin external granule cell layer ( J:92189 )

abnormal cerebellar Purkinje cell layer ( J:92189 )

• at P5 cells are dispersed in a thinner layer than in control Shh^tm2Amc/Shh^tm3Amc control mice or Shh^tm2Amc/Shh^tm3Amc;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 Shh^tm2Amc/Shh^tm3Amc;Tg(Pax2-cre)1Amc mice

decreased Purkinje cell number ( J:92189 )

• at P5 number is reduced by 20% compared to controls

• in adults, a 35% reduction is apparent

small cerebellum ( J:92189 )

• 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

Genotype
MGI:3759227

cn8

• Allelic Composition: Shh^tm1Amc/Shh^tm2Amc; Tg(Thy1-cre)703Vaw/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:78708 )

• mice die at birth

vision/eye

abnormal optic nerve morphology ( J:83530 )

• 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

abnormal eye development ( J:83530 )

• 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

microphthalmia ( J:78708 , J:83530 )

• as early as E13 (J:83530)

abnormal eyelid morphology ( J:83530 )

• eyelids fail to close throughout gestation

abnormal retina morphology ( J:78708 )

• 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

abnormal retina ganglion cell morphology ( J:83530 )

• 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

holoprosencephaly ( J:78708 , J:83530 )

• 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)

abnormal glial cell morphology ( J:83530 )

• glial progenitor cells are absent from the optic nerves

• the distal two thirds of optic nerves lack Pax2-expressing glial cells

abnormal retina ganglion cell morphology ( J:83530 )

• 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

abnormal optic nerve morphology ( J:83530 )

• 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

abnormal craniofacial morphology ( J:83530 )

growth/size/body

microcephaly ( J:83530 )

• as early as E13

Genotype
MGI:5441067

cn9

• Allelic Composition: Shh^tm1Amc/Shh^tm2Amc; Tg(Hoxb7-cre)13Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

renal/urinary system

abnormal renal glomerulus morphology ( J:79481 )

• 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

decreased renal glomerulus number ( J:79481 )

• newborn mice exhibit a 40% reduction in glomerular number

kidney cortex hypoplasia ( J:79481 )

• at the newborn stage, cortical volume is reduced by 51%

abnormal kidney inner medulla morphology ( J:79481 )

• at 4 months of age, most of the inner medulla is lost in hydronephric kidneys

abnormal kidney outer medulla inner stripe morphology ( J:79481 )

• at 4 months of age, most of the inner stripe of the outer medulla is lost in hydronephric kidneys

kidney medulla hypoplasia ( J:79481 )

• at the newborn stage, medullary volume is reduced by 46%

hydronephrosis ( J:79481 )

• at 4 months of age, 50% of mice exhibit hydronephrosis

• however, no hydronephrosis is detected in newborn pups

small kidney ( J:79481 )

• neonatal kidneys are 52% smaller than wild-type kidneys

renal hypoplasia ( J:79481 )

abnormal ureter development ( J:79481 )

• 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

abnormal ureter smooth muscle morphology ( J:79481 )

• 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

hydroureter ( J:79481 )

• newborn mice exhibit prominent hydroureter, usually more severe in the proximal region

short ureter ( J:79481 )

• at E14.5, ureter length is ~21% shorter than in wild-type controls

Genotype
MGI:5496012

cn10

• Allelic Composition: Shh^tm2Amc/Shh^tm2Amc; Tg(Atp4b-cre/ERT2)1Jrgo/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

digestive/alimentary system

digestive/alimentary phenotype ( J:191241 )

N • total parietal cell number remains unchanged following tamoxifen treatment

abnormal gastric surface mucous cell morphology ( J:191241 )

• 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

abnormal stomach pH ( J:191241 )

• parietal cells do not function in mutants treated with tamoxifen; parietal cells do not secrete acid in response to histamine stimulation

homeostasis/metabolism

delayed wound healing ( J:191241 )

• 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

cardiovascular system

abnormal physiological neovascularization ( J:191241 )

• 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

Genotype
MGI:3584381

cn11

• Allelic Composition: Shh^tm1Amc/Shh^tm2Amc; Tg(KRT14-cre)1Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

neonatal lethality, complete penetrance ( J:65294 )

• mutant newborns die within a day after birth

craniofacial

abnormal cranium morphology ( J:65294 )

• at birth, mutant pups display flattened skulls

absent alveolar process ( J:65294 )

• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent

abnormal incisor morphology ( J:65294 )

• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla

abnormal lower incisor morphology ( J:65294 )

• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted

small incisors ( J:65294 )

• at birth, incisors are only 5% of normal size

abnormal molar cusp morphology ( J:65294 )

• mandibular molars display a single irregular cusp; additional cusp formation is disrupted

small molars ( J:65294 )

• at birth, mutant pups display small and abnormally shaped first molars in both the mandible and maxilla

• maxillary molars are less affected than mandibular molars which are 25% of normal size

• although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed

absent enamel cord ( J:65294 )

• the dental cord is absent in mandibular molars

arrest of tooth development ( J:65294 )

• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology

growth retardation of incisors ( J:65294 )

• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars

growth retardation of molars ( J:65294 )

• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors

abnormal dentin morphology ( J:65294 )

• in grafts of early tooth rudiments (13.5-15.5 dpc), dentin deposits are deposited but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal odontoblast morphology ( J:65294 )

• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture

abnormal enamel morphology ( J:65294 )

• at 14.5 dpc, the outer enamel epithelium of the lingual side is severely reduced and the lingual inner enamel epithelium has not invaginated, suggesting impaired crown formation

• when early tooth rudiments (13.5-15.5 dpc) are transplanted under kidney capsules of nude mice, enamel matrix is secreted but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal ameloblast morphology ( J:65294 )

• 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

abnormal nasal bone morphology ( J:65294 )

• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced

abnormal palatal shelf fusion at midline ( J:90909 )

• the rudimentary palatal shelves are spaced widely apart

palatal shelf hypoplasia ( J:90909 )

• the palatal shelves fail to develop beyond rudimentary processes

cleft secondary palate ( J:90909 )

• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart

skeleton

skeleton phenotype ( J:65294 )

N • at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length

abnormal cranium morphology ( J:65294 )

• at birth, mutant pups display flattened skulls

absent alveolar process ( J:65294 )

• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent

abnormal incisor morphology ( J:65294 )

• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla

abnormal lower incisor morphology ( J:65294 )

• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted

small incisors ( J:65294 )

• at birth, incisors are only 5% of normal size

abnormal molar cusp morphology ( J:65294 )

• mandibular molars display a single irregular cusp; additional cusp formation is disrupted

small molars ( J:65294 )

• at birth, mutant pups display small and abnormally shaped first molars in both the mandible and maxilla

• maxillary molars are less affected than mandibular molars which are 25% of normal size

• although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed

absent enamel cord ( J:65294 )

• the dental cord is absent in mandibular molars

arrest of tooth development ( J:65294 )

• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology

growth retardation of incisors ( J:65294 )

• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars

growth retardation of molars ( J:65294 )

• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors

abnormal dentin morphology ( J:65294 )

• in grafts of early tooth rudiments (13.5-15.5 dpc), dentin deposits are deposited but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal odontoblast morphology ( J:65294 )

• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture

abnormal enamel morphology ( J:65294 )

• at 14.5 dpc, the outer enamel epithelium of the lingual side is severely reduced and the lingual inner enamel epithelium has not invaginated, suggesting impaired crown formation

• when early tooth rudiments (13.5-15.5 dpc) are transplanted under kidney capsules of nude mice, enamel matrix is secreted but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal ameloblast morphology ( J:65294 )

• 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

abnormal nasal bone morphology ( J:65294 )

• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced

vision/eye

eyelids open at birth ( J:65294 )

respiratory system

abnormal nasal bone morphology ( J:65294 )

• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:90909 )

• the rudimentary palatal shelves are spaced widely apart

palatal shelf hypoplasia ( J:90909 )

• the palatal shelves fail to develop beyond rudimentary processes

cleft secondary palate ( J:90909 )

• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart

aerophagia ( J:65294 )

• at birth, mutant pups are observed gulping air

integument

absent vibrissae ( J:65294 )

growth/size/body

absent alveolar process ( J:65294 )

• mutant mandibular molars are fused with the oral ectoderm and the alveolar bone is absent

abnormal incisor morphology ( J:65294 )

• at birth, mutant pups display small (only 5% of normal size) and abnormally shaped incisors in both the mandible and maxilla

abnormal lower incisor morphology ( J:65294 )

• mandibular incisors display a single cusp with two symmetrical cervical loops; additional cusp formation is disrupted

small incisors ( J:65294 )

• at birth, incisors are only 5% of normal size

abnormal molar cusp morphology ( J:65294 )

• mandibular molars display a single irregular cusp; additional cusp formation is disrupted

small molars ( J:65294 )

• at birth, mutant pups display small and abnormally shaped first molars in both the mandible and maxilla

• maxillary molars are less affected than mandibular molars which are 25% of normal size

• although cervical loops, dental papilla, inner enamel epithelium, predentin, and stellate reticulum are present, no dental cord is formed

absent enamel cord ( J:65294 )

• the dental cord is absent in mandibular molars

arrest of tooth development ( J:65294 )

• at birth, mutant pups show absence of obvious teeth: manidbular molars and incisors exhibit a cap stage tooth rudiment of abnormal morphology

growth retardation of incisors ( J:65294 )

• at birth, mandibular incisors are more developmentally advanced relative to mandibular molars

growth retardation of molars ( J:65294 )

• at birth, mandibular molars are less developmentally advanced relative to mandibular incisors

abnormal dentin morphology ( J:65294 )

• in grafts of early tooth rudiments (13.5-15.5 dpc), dentin deposits are deposited but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal odontoblast morphology ( J:65294 )

• at birth, functional odontoblast layers are present but display abnormal polarity and cellular architecture

abnormal enamel morphology ( J:65294 )

• at 14.5 dpc, the outer enamel epithelium of the lingual side is severely reduced and the lingual inner enamel epithelium has not invaginated, suggesting impaired crown formation

• when early tooth rudiments (13.5-15.5 dpc) are transplanted under kidney capsules of nude mice, enamel matrix is secreted but crown formation is incomplete and resulting teeth are small and abnormally shaped

abnormal ameloblast morphology ( J:65294 )

• 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

abnormal nasal bone morphology ( J:65294 )

• at birth, mutant pups display a small frontal nasal process; nasal passageways are severely reduced

abnormal palatal shelf fusion at midline ( J:90909 )

• the rudimentary palatal shelves are spaced widely apart

palatal shelf hypoplasia ( J:90909 )

• the palatal shelves fail to develop beyond rudimentary processes

cleft secondary palate ( J:90909 )

• 85% exhibit a cleft palate with rudimentary palatal shelves spaced widely apart

Genotype
MGI:4889096

cn12

• Allelic Composition: Shh^tm2Amc/Shh^tm2.1Amc; Tg(Nr5a1-cre)2Klp/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:168522 )

• adrenal glands exhibit a decrease in stem/precursor cells compared with wild-type mice

abnormal adrenocortical cell morphology ( J:168522 )

• the number of adrenocortical cells is decreased while their size is increased compared to in wild-type mice

enlarged adrenocortical cells ( J:168522 )

thin adrenal cortex ( J:168522 )

small adrenal glands ( J:168522 )

• at P5

abnormal adrenal gland physiology ( J:168522 )

• at E16.5 and P5, adrenal gland cells exhibit reduced proliferation compared with wild-type cells

homeostasis/metabolism

decreased circulating corticosterone level ( J:168522 )

• at P21

increased circulating adrenocorticotropin level ( J:168522 )

Genotype
MGI:5550094

cn13

• Allelic Composition: Gata6^tm2.1Sad/Gata6^tm2.1Sad; Shh^tm2Amc/Shh^tm2Amc; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL/J

limbs/digits/tail

hindlimb oligodactyly ( J:205405 )

• hindlimbs have four digits

Genotype
MGI:3617985

cn14

• Allelic Composition: Shh^tm2Amc/Shh^tm2Amc; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:102950 )

• death by P15

growth/size/body

microcephaly ( J:102950 )

decreased body size ( J:147427 )

• animals are smaller than littermates, but are postnatally viable and have relatively normal gross morphology

postnatal growth retardation ( J:102950 )

• marked reduction in growth by the second postnatal week

nervous system

seizures ( J:102950 )

• pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week

abnormal brain interneuron morphology ( J:102950 )

• reductions of somatostatin- and parvalbumin-expressing interneurons in somatosensory cortex

• somatostatin- and Npy-expressing interneurons are also reduced in the striatum

decreased brain size ( J:102950 , J:147427 )

• 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)

disorganized thalamus ( J:147427 )

• thalamus organization is disrupted in mutants based on molecular marker analysis

abnormal medial ganglionic eminence morphology ( J:102950 )

• 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

behavior/neurological

seizures ( J:102950 )

• pronounced extension of the hindlimbs in response to handling and seizure-like behavior by the second postnatal week

Genotype
MGI:3051583

cn15

• Allelic Composition: Shh^tm2Amc/Shh^tm2Amc; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:91723 )

• mutants die shortly after birth when doxycycline is administered throughout gestation

• in the absence of doxycycline mutants are viable

respiratory system

abnormal lung morphology ( J:91723 )

• 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

lung cyst ( J:91723 )

• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue

abnormal branching involved in lung morphogenesis ( J:91723 )

• branching morphogenesis is abnormal

pulmonary hypoplasia ( J:91723 )

• lungs are hypoplastic when doxycycline is administered throughout gestation

abnormal bronchus morphology ( J:91723 )

• peripheral tubule dilation is seen after doxycycline exposure

abnormal trachea morphology ( J:91723 )

• tracheal abnormalities are seen

• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities

abnormal tracheal cartilage morphology ( J:91723 )

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

decreased tracheal cartilage ring number ( J:91723 )

• fewer cartilaginous rings are seen after doxycycline exposure

skeleton

abnormal tracheal cartilage morphology ( J:91723 )

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

decreased tracheal cartilage ring number ( J:91723 )

• fewer cartilaginous rings are seen after doxycycline exposure

growth/size/body

lung cyst ( J:91723 )

• cysts that contain neuroepithelial cells are seen in the peripheral lung tissue

Genotype
MGI:3051584

cn16

• Allelic Composition: Shh^tm1Amc/Shh^tm2Amc; Tg(SFTPC-rtTA)5Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:91723 )

• mutants die shortly after birth when doxycycline is administered throughout gestation

• in the absence of doxycycline treatment mutants are viable

respiratory system

abnormal lung morphology ( J:91723 )

• 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

lung cyst ( J:91723 )

• cysts are seen in the peripheral lung tissue

abnormal branching involved in lung morphogenesis ( J:91723 )

• branching morphogenesis is abnormal with doxycycline treatment

pulmonary hypoplasia ( J:91723 )

• lungs are hypoplastic after doxycycline exposure

abnormal bronchus morphology ( J:91723 )

• peripheral tubule dilation is seen with doxycycline exposure

abnormal trachea morphology ( J:91723 )

• tracheal abnormalities are seen

• doxycycline exposure before E8.5 or after E13.5 does not result in tracheal abnormalities

abnormal tracheal cartilage morphology ( J:91723 )

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

decreased tracheal cartilage ring number ( J:91723 )

• fewer cartilaginous rings are seen with doxycycline treatment

skeleton

abnormal tracheal cartilage morphology ( J:91723 )

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

decreased tracheal cartilage ring number ( J:91723 )

• fewer cartilaginous rings are seen with doxycycline treatment

growth/size/body

lung cyst ( J:91723 )

• cysts are seen in the peripheral lung tissue