Mouse Genome Informatics
hm1
    Shhtm1Amc/Shhtm1Amc
involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
hm2
    Shhtm1Amc/Shhtm1Amc
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis

nervous system

skeleton
• all ventral vertebral components are absent


Mouse Genome Informatics
hm3
    Shhtm1Amc/Shhtm1Amc
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
hm4
    Shhtm1Amc/Shhtm1Amc
STOCK Shhtm1Amc/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
ht5
    Shhtm1Amc/Shhtm1.1Rseg
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
N
• while organ size is reduced to various degrees, all organs are present and correctly localized unlike in Shh-null mice (J:150524)

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


Mouse Genome Informatics
ht6
    Shhtm1Amc/Shhtm2Amc
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• compound heterozygotes for Shhtm1Amc and Shhtm2Amc are viable and fertile with no discernible phenotype


Mouse Genome Informatics
ht7
    Shhtm1.1Dje/Shhtm1Amc
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:170540)
• dead pups often have milk in their stomach (J:170540)
• well coordinated motor control (J:170540)

homeostasis/metabolism
N
• normal blood glucose (J:170540)


Mouse Genome Informatics
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
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
cn9
    Disp1icb/Disp1icb
Shhtm1Amc/Shhtm5Amc
Tg(Sox2-cre)1Amc/0

involves: 129/Sv * C57BL/6J * SWR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
cn10
    Shhtm1Amc/Shhtm2Amc
Tg(Thy1-cre)703Vaw/?

involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at birth

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


Mouse Genome Informatics
cn11
    Shhtm1Amc/Shhtm2Amc
Tg(Hoxb7-cre)13Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
cn12
    Shhtm1Amc/Shhtm2Amc
Tg(KRT14-cre)1Amc/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 a small frontal nasal process; nasal passageways are severely reduced
• 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
• 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
• 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
• 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

skeleton
N
• at birth, mutant pups possess normal skeletal elements; the upper and lower jaws are of normal length (J:65294)
• 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 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, 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
• 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
• 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
• 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


Mouse Genome Informatics
cn13
    Shhtm1Amc/Shhtm2Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0

involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
cx14
    Ihhtm1Amc/Ihhtm1Amc
Shhtm1Amc/Shhtm1Amc

involves: 129/Sv * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• double homozygotes arrest at early somite stages


Mouse Genome Informatics
cx15
    Disp1tm2.1Amc/Disp1tm2.1Amc
Shhtm1Amc/Shh+

involves: 129/Sv * C57BL/6J * SWR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

embryogenesis
• 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


Mouse Genome Informatics
cx16
    Nr5a1tm1.1Hain/Nr5a1tm1.1Hain
Shhtm1Amc/Shh+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• decreased adrenal aldosterone levels
• decrease is less severe than in mice homozygous for Nr5a1tm1.1Hain alone


Mouse Genome Informatics
cx17
    Disp1icb/Disp1tm1Amc
Shhtm1Amc/Shh+

involves: 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 IDRef(s)
Holoprosencephaly 3; HPE3 142945 J:92058


Mouse Genome Informatics
cx18
    Shhtm1Amc/Shhtm1Amc
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-Shh)1Jaw/0

involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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