Mouse Genome Informatics
hm1
    Gli2tm1Alj/Gli2tm1Alj
either: (involves: 129S1/Sv * 129X1/Sv) or (involves: 129S1/Sv * 129X1/Sv * CD-1)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozygotes are stillborn; resorbed embryos often found at late gestational stages

embryogenesis
• visible at E10.5

growth/size
• visible at E10.5

hearing/vestibular/ear
• tympanic ring bones are missing in some homozygotes

homeostasis/metabolism
• at E14.5 subcutaneous edema can be seen in the back

craniofacial
• a deficiency of the medial portion of frontal and parietal bones is observed
• a deficiency of the medial portion of frontal and parietal bones is observed
• in cases of severe cleft palate the presphenoid bone is absent
• lower jaw appears normal, but is reduced in size
• missing in severe cases of cleft palate
• truncation of distal maxilla is seen
• missing in severe cases of cleft palate
• cleft palate is seen at birth with 64% penetrance
• in severely affected embryos, mutant palatal shelves were either do not elevate at all or only partially elevate
• in less severely affected embryos, the mutant shelves do elevate but show a delay in fusion
• 91% of animals lack upper incisors; 33% are missing lower incisors
• at E14.5 head appears to be flattened
• seen at E10.5

skeleton
• a deficiency of the medial portion of frontal and parietal bones is observed
• a deficiency of the medial portion of frontal and parietal bones is observed
• in cases of severe cleft palate the presphenoid bone is absent
• lower jaw appears normal, but is reduced in size
• missing in severe cases of cleft palate
• truncation of distal maxilla is seen
• missing in severe cases of cleft palate
• length of sternum is reduced
• bilateral pair of extra ribs are present in 36% and a unilateral extra rib occurs in 6%
• intervertebral disks are absent or reduced
• vertebral column often displayed a bend in the thoracic-lumbar region
• ossification of vertebral bodies is reduced or absent
• ossification of the skull is delayed;
• 100% of skeletons lacked ossification of digits at E17.5; 53% had no ossification of the digits at E18.5
• ossification of the humerus, ulna, radius, femur, fibula, and tibia is reduced to 75%, 85%, 50%, 85%, 75%, and 60% of wild-type, respectively
• little or no ossification of the vertebral bodies is seen; however, ossification of the neural arches is normal

limbs/digits/tail

digestive/alimentary system
• missing in severe cases of cleft palate
• missing in severe cases of cleft palate
• cleft palate is seen at birth with 64% penetrance
• in severely affected embryos, mutant palatal shelves were either do not elevate at all or only partially elevate
• in less severely affected embryos, the mutant shelves do elevate but show a delay in fusion


Mouse Genome Informatics
hm2
    Gli2tm1Alj/Gli2tm1Alj
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• near absence ofV3 neurons in the thoracic region of the spinal cord at E10.5

cellular
• near absence ofV3 neurons in the thoracic region of the spinal cord at E10.5


Mouse Genome Informatics
hm3
    Gli2tm1Alj/Gli2tm1Alj
involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• at E16.5 and E18.5, the temporomandibular condyle is much smaller in size with loss of growth plate organization unlike in wild-type mice
• chondroprogenitor cells and prehypertrophic chondrocytes are reduced in number compared to in wild-type mice
• at E16.5, E18.5, and P0, the temporomandibular joint disk is missing unlike in wild-type mice
• at E18.5, the lower temporomandibular joint cavity is not visible unlike in wild-type mice
• cells within the growth plate of the temporomandibular condyle are larger in size and disorganized compared to in wild-type mice

craniofacial
• at E16.5 and E18.5, the temporomandibular condyle is much smaller in size with loss of growth plate organization unlike in wild-type mice


Mouse Genome Informatics
hm4
    Gli2tm1Alj/Gli2tm1Alj
involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• at E10.5 and E11.5, the primary branching of the right lung is impaired; however, the left lung develops normally
• at E14.5, but not at E11.5, mutant lungs show a 40% and 25% reduction in the number proliferating (BrdU+) cells in the mesenchymal and epithelial compartments, respectively
• at E18.5, mutant terminal air sacs are smaller and lined by thicker interstitial layers
• however, mutant epithelial cells can undergo terminal differentiation
• at E14.5, but not at E11.5, mutant lungs show a 40% reduction in the number proliferating (BrdU+) cells in the mesenchymal compartment
• at E18.5, mutant terminal air sacs are smaller and lined by thicker interstitial layers
• at E18.5, mutant interstitial mesenchymal cell layers are thicker than normal
• at E18.5, the density of surfactant protein C (a marker for mature alveolar type II cells)-positive cells is increased relative to that in wild-type controls
• at E10.5 and E11.5, mutant lungs are significantly smaller than wild-type
• at E13.5 and E18.5, the wet weight of the mutant left lung is ~60% and 50% of that in wild-type and heterozygous controls, respectively
• lung hypoplasia is likely due to reduced cell proliferation at later stages of lung development
• no differences in apoptotic cell death are observed relative to wild-type controls
• at E10.5 and E11.5, a one-lobed right lung is observed, unlike the four-lobed right lung seen in wild-type embryos
• at E18.5, the cartilaginous rings of the mutant trachea are smaller and split in some cases
• at E18.5, the mutant trachea is hypoplastic
• at E18.5

digestive/alimentary system
• the mutant esophagus fails to develop a smooth muscle layer
• homozygotes display foregut malformations, including stenosis of the esophagus and trachea, lung hypoplasia and lung lobulation defects
• at E18.5, the mutant esophagus lacks smooth muscle
• at E18.5
• at E18.5, the mutant esophagus is hypoplastic with a very small lumen that lacks the typical folded structure seen in wild-type controls

nervous system
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice

embryogenesis
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice

muscle
• at E18.5, the mutant esophagus lacks smooth muscle

skeleton
• at E18.5, the cartilaginous rings of the mutant trachea are smaller and split in some cases

cellular
• at E14.5, but not at E11.5, mutant lungs show a 40% reduction in the number proliferating (BrdU+) cells in the mesenchymal compartment


Mouse Genome Informatics
hm5
    Gli2tm1Alj/Gli2tm1Alj
involves: 129S1/Sv * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lethality at birth is observed

nervous system
• cerebellum has abnormal foliation that is more pronounced posteriorly; foliation is reduced
• in anterior and posterior regions of cerebellum, external granule layer (EGL) contains only 2-4 cell layers in contrast to wild-type where there are 5-8 layers
• smaller than in wild-type


Mouse Genome Informatics
ht6
    Gli2tm1Alj/Gli2+
involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice

embryogenesis
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice


Mouse Genome Informatics
ht7
    Gli2tm1Alj/Gli2tm2.1Alj
either: (involves: 129) or (involves: 129 * Black Swiss)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E10.5 cells that express Shh and Foxa2 are absent
• at E10.5 motor neurons occupy the ventral midline of the spinal cord
• the notochord is situated closer to the spinal cord
• decrease in the number of spinal cord V3 interneurons that are normally adjacent to the floor plate at E10.5

embryogenesis
• at E10.5 cells that express Shh and Foxa2 are absent
• at E10.5 cells that express Shh and Foxa2 are absent
• the notochord is situated closer to the spinal cord
• the notochord fails to regress

respiratory system
• the accessory lobe is absent


Mouse Genome Informatics
ht8
    Gli2tm1Alj/Gli2tm6.1Alj
involves: 129/Sv * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lethality at birth is observed

embryogenesis
• at E10.5, patterning of ventral spinal cord is abnormal
• at E18.5, body axis is curved

nervous system
• cerebellum has abnormal foliation that is more pronounced posteriorly; foliation is reduced
• in anterior and posterior regions of cerebellum, external granule layer (EGL) contains only 2-4 cell layers in contrast to wild-type where there are 5-8 layers
• seen in E18.5 embryos
• smaller than in wild-type


Mouse Genome Informatics
ht9
    Gli2tm5(GLI3)Alj/Gli2tm1Alj
involves: 129S1/Sv * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• phenotype is similar to that of Gli2tm1Alj mutant embryos, indicating that a low level of Gli3 is not enough to substitute for Gli2
• absence of floor plate cells throughout the anterior/posterior (A/P) axis of the spinal cord

nervous system
• phenotype is similar to that of Gli2tm1Alj mutant embryos, indicating that a low level of Gli3 is not enough to substitute for Gli2
• absence of floor plate cells throughout the anterior/posterior (A/P) axis of the spinal cord


Mouse Genome Informatics
cn10
    Gli2tm1Alj/Gli2tm6Alj
Tg(Nes-cre)1Kln/0

involves: 129/Sv * C57BL/6 * SJL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• foliation occurs to a greater extent, with the vermis having a more defined intercrural structure and thicker IGL than in Gli2;En1 conditional knockouts


Mouse Genome Informatics
cn11
    En1tm2(cre)Gld/En1+
Gli2tm1Alj/Gli2tm6Alj

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• adults are ~75% of size of wild-type littermates

behavior/neurological
• mice show deficits in motor control such as intention tremors consistent with cerebellar defects
• mutants have balance problems
• mice have a wide-based gait

nervous system
N
• cerebella are similar in volume and thickness to wild-type at E16.5 and do not show the same defects as non-conditional Shh-null animals at that time point (J:108507)
• number of lobules in addition to cardinal lobes in vermis and hemispheres is greatly reduced compared to wild-type
• at birth, EGL of mutants is only one or two cell layers thick compared to 2-4 layers in wild-type; at P5, EGL is only 1 to 4 layers thick compared to 8 to 10 in wild-type
• difference is more apparent at the base of fissures than at crown of lobe
• reduced thickness correlates with delayed onset of foliation and reduced complexity
• at birth, EGL of mutants is only one or two cell layers thick compared to 2-4 layers in wild-type; at P5, EGL is only 1 to 4 layers thick compared to 8 to 10 in wild-type
• difference is more apparent at the base of fissures than at crown of lobe
• reduced thickness correlates with delayed onset of foliation and reduced complexity
• Purkinje cells (PCs) remain multilayered in mutants instead of forming a monolayer as in wild-type
• glial fibers of Bergmann glia are misshapen and disorganized compared to linear, ordered morphology in wild-type
• internal granule layer (IGL) is thinner compared to wild-type
• dendritic arborization of PCs in molecular layer is less branched than normal
• central lobe is divided by a shallow fissure
• fissure dividing anterobasal lobe is absent or shallow in most mutant brains
• adult brains show an extreme decrease in size compared to wild-type while rest of brain appears normal in size
• mediolateral (ML) extent is not as drastically reduced in length compared with anteroposterior (AP) axis
• cerebellum does not increase in size after P8 while in wild-type it grows until P16; only slight growth occurs between P5 and P8; surface area is reduced


Mouse Genome Informatics
cn12
    En1tm2(cre)Gld/En1+
Gli1tm2Alj/Gli1tm2Alj
Gli2tm1Alj/Gli2tm6Alj

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• cerebellum has decreased number of fissures compared to conditional Gli2 knockouts
• only the five cardinal lobes of cerebellum can be discerned; other lobules do not form
• decreased number of lobules (abnormal foliation) is observed


Mouse Genome Informatics
cx13
    Gli1tm2Alj/Gli1+
Gli2tm1Alj/Gli2tm1Alj
Gli3Xt/Gli3Xt

involves: 101/H * 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H/HeH * C57BL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• progenitors for motor neurons, V1 and V2 interneurons are present but intermixed indicating abnormal spatial patterning
• incorrect positioning and number of V0-V2 and motor neuron progenitors at E9.5
• increased proliferation of ventral spinal cord progenitors at E10.5
• floor plate progenitors are missing
• ventral spinal cord is expanded resulting in a wavy appearance
• distribution of motor neurons varies at E12.5
• reduction in the number of differentiated motor neurons but an increase in their progenitors
• absence of V3 progenitors and interneurons, however V0-V2 cells are formed
• fewer V2, V1, and V0 interneurons are seen in the hindlimb

embryogenesis
• floor plate progenitors are missing

cellular
• progenitors for motor neurons, V1 and V2 interneurons are present but intermixed indicating abnormal spatial patterning
• incorrect positioning and number of V0-V2 and motor neuron progenitors at E9.5
• increased proliferation of ventral spinal cord progenitors at E10.5


Mouse Genome Informatics
cx14
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt/Gli3+

involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the motor neuron progenitor domain is greatly expanded dorsally however motor neurons appear to differentiate normally

cellular
• the motor neuron progenitor domain is greatly expanded dorsally however motor neurons appear to differentiate normally


Mouse Genome Informatics
cx15
    Gli2tm1Alj/Gli2+
Gli3Xt/Gli3Xt

involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the motor neuron progenitor domain is greatly expanded dorsally however motor neuron appear to differentiate normally

cellular
• the motor neuron progenitor domain is greatly expanded dorsally however motor neuron appear to differentiate normally


Mouse Genome Informatics
cx16
    Gli1tm2Alj/Gli1tm2Alj
Gli2tm1Alj/Gli2+

involves: 129/Sv * Black Swiss * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• at E10.5, some floor plate cells have been lost
• in severely affected embryos, Foxa2-expressing cells are absent; Nkx2-2 interneurons are greatly reduced
• motor neurons occupy a more ventral position compared to controls

nervous system
• at E10.5, some floor plate cells have been lost
• in severely affected embryos, Foxa2-expressing cells are absent; Nkx2-2 interneurons are greatly reduced
• motor neurons occupy a more ventral position compared to controls

respiratory system


Mouse Genome Informatics
cx17
    Gli1tm2Alj/Gli1tm2Alj
Gli2tm1Alj/Gli2tm1Alj

involves: 129/Sv * Black Swiss * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• lungs have only 2 lobes at E12.5
• at E12.5 and E18.5, lungs are smaller than in Gli2tm1Alj homozygotes and much smaller than wild-type

limbs/digits/tail
• at E18.5 a postaxial nubbin is present on mutant limbs


Mouse Genome Informatics
cx18
    Gli2tm1Alj/Gli2+
Kif7tm1.2Hui/Kif7tm1.2Hui

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice

embryogenesis
• expression of ventral neural tube patterning markers is altered compared to in wild-type mice


Mouse Genome Informatics
cx19
    Gli2tm1Alj/Gli2tm1Alj
Pax6Sey/Pax6Sey

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic region similar to Pax6 single homozygotes

cellular
• at E10.5 Nkx2.2+ V3 progenitors show dorsal expansion in the thoracic region similar to Pax6 single homozygotes


Mouse Genome Informatics
cx20
    Gli1tm2Alj/Gli1+
Gli2tm1Alj/Gli2tm1Alj

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• at E12.5 lungs are smaller than in wild-type


Mouse Genome Informatics
cx21
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt-J/Gli3Xt-J

involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double homozygotes die before E10.5


Mouse Genome Informatics
cx22
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt-J/Gli3+

involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
craniofacial
• coronoid, condylar, angular and dental processes are hypoplastic

limbs/digits/tail
• on forelimbs, there is a postaxial stub of an extra digit
• display more severe preaxial polydactyly compared to Gli2 homozygotes
• shortening of the humerus
• shortening of the radius; shortening is more severe than in the ulna
• shortening of the ulna, although not as severe as the radius
• not as severe as the tibia

skeleton
• show an exacerbated phenotype in various skeletal elements with respect to Gli2 nulls
• coronoid, condylar, angular and dental processes are hypoplastic
• shortening of the humerus
• shortening of the radius; shortening is more severe than in the ulna
• shortening of the ulna, although not as severe as the radius
• not as severe as the tibia
• sternum is split rostrally and improperly segmented
• there are severe abnormalities in chondrogenesis of ventral vertebral components
• there are severe abnormalities in chondrogenesis of ventral vertebral components


Mouse Genome Informatics
cx23
    Gli2tm1Alj/Gli2+
Gli3Xt-J/Gli3Xt-J

involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
skeleton
• show an enhancement of the Gli3 null phenotype
• neural arches of other cervical vertebrae are fused in addition to the fusion of the C1 and C2 neural arches

limbs/digits/tail


Mouse Genome Informatics
cx24
    Gli2tm1Alj/Gli2+
Gli3Xt-J/Gli3+

involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
limbs/digits/tail
• not different from Gli3 heterozygotes


Mouse Genome Informatics
cx25
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt-J/Gli3Xt-J

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• reduced numbers of motor neurons in the thoracic and lumbar cord of embryos
• motor neuron progenitors shifted to more ventral locations and increased 20% in thoracic region while being reduced about 15% in lumbar region
• V3 interneurons absent in thoracic and lumbar spinal cord of embryos
• V1, V2a, and V2b interneurons expand down tointo the ventral midline becoming intermingled with one another and with motor neurons in embryos
• V2 interneurons are reduced in number in embryos
• V0 interneurons are normal but increased in numbers in embryos
• V1 interneurons are also increased in numbers but only in the thoracic region of embryos


Mouse Genome Informatics
cx26
    Gli2tm1Alj/Gli2tm1Alj
Ift122sopb/Ift122sopb

involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
embryogenesis
• patterning resembles that in mice homozygous for Gli2tm1Alj alone

nervous system
• patterning resembles that in mice homozygous for Gli2tm1Alj alone


Mouse Genome Informatics
cx27
    Gli2tm1Alj/Gli2tm1Alj
Kif7maki/Kif7maki
Tg(Hlxb9-GFP)1Tmj/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• unlike in Kif7 single mutants, in compound mutants the motor neuron domain is not expanded dorsally and the Nkx2.2+ domain is absent

embryogenesis
• unlike in Kif7 single mutants, in compound mutants the motor neuron domain is not expanded dorsally and the Nkx2.2+ domain is absent


Mouse Genome Informatics
cx28
    Gli1tm1Alj/Gli1tm1Alj
Gli2tm1Alj/Gli2tm1Alj

involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no double homozygotes survive past birth
• fewer than expected double homozygotes are seen at E18.5

nervous system
• at E12.5, pituitary gland is absent
• dorsal and ventral regions of the telencephalon appeared abnormal
• neural epithelium is thickened in telencephalic region
• motor neurons are induced in the ventral midline of the spinal cord, similar to Gli2 single homozygotes

endocrine/exocrine glands
• at E12.5, pituitary gland is absent

respiratory system
• at E12.5, the 2 lobes are similar in size and planar
• at E12.5 and 18.5, only one very small lobe is present bilaterally; however, branching is visible in the lobes

limbs/digits/tail
• at E15.5 and 18.5 all four limbs had five digits; however an extra postaxial stub of a digit is present


Mouse Genome Informatics
cx29
    Gli1tm1Alj/Gli1tm1Alj
Gli2tm1Alj/Gli2+

involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die shortly after birth with only 3.8% surviving to weaning age

embryogenesis
• variable loss of cells expressing floor plate markers is seen in 2 of 5 mice in random patches in the posterior regions
• at E12.5 and 14, notochord has not regressed from the ventral spinal cord

growth/size
• animals which survive to weaning are smaller

endocrine/exocrine glands
(J:60986)

behavior/neurological
• animals unable to right themselves
• hopping gait

nervous system
• variable loss of cells expressing floor plate markers is seen in 2 of 5 mice in random patches in the posterior regions
• motor neurons are located closer to the midline than normal

respiratory system
• at E18.5, the left lobe is reduced in width
• at E12.5, slight reduction in size of accessory lobe visible
• at E18.5, the accessory lobe is reduced in length and in width
• at E18.5, the right cranial lobe is reduced in length

reproductive system
(J:60986)
• external genitalia are incompletely developed (J:60986)

digestive/alimentary system
• at 5-7 weeks of age the gut is distended


Mouse Genome Informatics
cx30
    Gli1tm1Alj/Gli1+
Gli2tm1Alj/Gli2tm1Alj

involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• at E12.5 and E18.5, lungs appear to have 2 small lobes
• at E12.5 and E18.5, lungs appear smaller than normal


Mouse Genome Informatics
cx31
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt/Gli3+

involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• at E11.5, mutant embryos display esophageal atresia with tracheoesophageal fistula, in which the esophagus is missing and the trachea is directly connected to the stomach
• at E16.5, the left and right lobes are fused, resulting in a single-lobed lung
• at E16.5, mutant lungs fail to separate into right and left lobes and are thus composed of a single lobe, whereas wild-type and homozygous Gli2tm1Alj mutant lungs have five and two lobes, respectively
• mutant lung buds do not form until E10.0, unlike in wild-type and homozygous Gli2tm1Alj mutant embryos where a pair of lung buds can be seen at E9.5
• at E11.5, an ectopic lung bud is found between the right and left lung buds
• at E16.5, mutant lungs are more hypoplastic than those of wild-type or homozygous Gli2tm1Alj mutant embryos
• at E16.5, the tracheal cartilaginous rings are more severely malformed than those in Gli2tm1Alj mutant embryos
• at E16.5, tracheal stenosis is more severe than that in Gli2tm1Alj mutant lungs

digestive/alimentary system
• at E11.5, mutant embryos display esophageal atresia with tracheoesophageal fistula
• at E11.5, mutant embryos display esophageal atresia with tracheoesophageal fistula, in which the esophagus is missing and the trachea is directly connected to the stomach

skeleton
• at E16.5, the tracheal cartilaginous rings are more severely malformed than those in Gli2tm1Alj mutant embryos


Mouse Genome Informatics
cx32
    Gli2tm1Alj/Gli2tm1Alj
Gli3Xt/Gli3Xt

involves: 129S1/Sv * 129X1/SvJ * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most double homozygous mutants die at ~E10.5
• a small number of double homozygous mutants survive to E13.5-E14.5

respiratory system
• no lung primordia are detected at E9.5 or later
• all double homozygous mutant mice lack lungs
• no tracheal primordia are detected at E9.5 or later
• all double homozygous mutant mice lack a trachea

digestive/alimentary system
• no esophageal primordia are detected at E9.5 or later
• no foregut differentiation into esophagus, trachea and lung is noted at E10.5
• at E10.5, the double mutant foregut endoderm remains a single tube, except for the stomach region
• all double homozygous mutant mice lack an esophagus

embryogenesis
• the foregut endoderm fails to develop into lung, trachea and esophagus
• however, hepatic and pancreatic buds are present


Mouse Genome Informatics
cx33
    Gli2tm1Alj/Gli2tm1Alj
Ptch1tm1Mps/Ptch1tm1Mps

involves: 129S1/Sv * 129X1/SvJ * Swiss Webster
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some embryos survive to E10.5; at E11.5, no embryos are recovered

nervous system
• at E10.5 dorsal brain has not closed
• embryos found at E10.5 exhibit exencephaly
• only small number of V3 interneurons remain in ventral midline of spinal cord at E9.5
• more motor neurons are generated than in Gli2-null mutants; motor neuron population expands into dorsal half of spinal cord
• number of V3 interneurons is reduced compared to Ptc-null embryos at E9.5