Phenotypes associated with this allele

• Allele Symbol: Gli2^tm1Alj
• Allele Name: targeted mutation 1, Alexandra L Joyner
• Allele ID: MGI:1857509
• Summary: 35 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gli2^tm1Alj/Gli2^tm1Alj	either: (involves: 129S1/Sv * 129X1/Sv) or (involves: 129S1/Sv * 129X1/Sv * CD-1)	MGI:2176889
hm2	Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ	MGI:2676436
hm3	Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * FVB/N	MGI:4366500
hm4	Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2166993
hm5	Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3665552
ht6	Gli2^tm1Alj/Gli2^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:4357968
ht7	Gli2^tm1Alj/Gli2^tm2.1Alj	either: (involves: 129) or (involves: 129 * Black Swiss)	MGI:2173471
ht8	Gli2^tm5(GLI3)Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:4414941
ht9	Gli2^tm1Alj/Gli2^tm6.1Alj	involves: 129/Sv * C57BL/6 * SJL	MGI:3665554
cn10	En1^tm2(cre)Gld/En1^+ Gli2^tm1Alj/Gli2^tm6Alj	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3665558
cn11	En1^tm2(cre)Gld/En1^+ Gli1^tm2Alj/Gli1^tm2Alj Gli2^tm1Alj/Gli2^tm6Alj	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3665567
cn12	Gli2^tm1Alj/Gli2^tm6Alj Tg(Nes-cre)1Kln/0	involves: 129/Sv * C57BL/6 * SJL * Swiss Webster	MGI:3665562
cx13	Gli1^tm2Alj/Gli1^+ Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt/Gli3^Xt	involves: 101/H * 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster	MGI:4414944
cx14	Gli2^tm1Alj/Gli2^+ Gli3^Xt/Gli3^Xt	involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster	MGI:4414948
cx15	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt/Gli3^+	involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster	MGI:4414946
cx16	Gli1^tm2Alj/Gli1^tm2Alj Gli2^tm1Alj/Gli2^+	involves: 129 * Black Swiss * Swiss Webster	MGI:2676433
cx17	Gli2^tm1Alj/Gli2^+ Kif7^tm1.2Hui/Kif7^tm1.2Hui	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * CD-1	MGI:4357967
cx18	Cdk20^tm1.1Jegg/Cdk20^tm1.1Jegg Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N	MGI:6113534
cx19	Gli2^tm1Alj/Gli2^tm1Alj Pax6^Sey/Pax6^Sey	involves: 129S1/Sv * 129X1/SvJ	MGI:3664781
cx20	Gli1^tm2Alj/Gli1^+ Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * Swiss Webster	MGI:3795863
cx21	Gli2^tm1Alj/Gli2^+ Gli3^Xt-J/Gli3^+	involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1	MGI:3614416
cx22	Gli2^tm1Alj/Gli2^+ Gli3^Xt-J/Gli3^Xt-J	involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1	MGI:3614413
cx23	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt-J/Gli3^+	involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1	MGI:2678685
cx24	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt-J/Gli3^Xt-J	involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1	MGI:2176890
cx25	Gli2^tm1Alj/Gli2^tm1Alj Ift122^sopb/Ift122^sopb	involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J	MGI:4888267
cx26	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt-J/Gli3^Xt-J	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * Swiss Webster	MGI:3052545
cx27	Ankmy2^tm1b(EUCOMM)Hmgu/Ankmy2^tm1b(EUCOMM)Hmgu Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N	MGI:6489571
cx28	Gli2^tm1Alj/Gli2^tm1Alj Kif7^maki/Kif7^maki Tg(Hlxb9-GFP)1Tmj/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:4355988
cx29	Gli1^tm1Alj/Gli1^tm1Alj Gli2^tm1Alj/Gli2^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3579188
cx30	Gli1^tm1Alj/Gli1^tm1Alj Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3579187
cx31	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt/Gli3^+	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:4936754
cx32	Gli2^tm1Alj/Gli2^tm1Alj Gli3^Xt/Gli3^Xt	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:4936829
cx33	Gli1^tm1Alj/Gli1^+ Gli2^tm1Alj/Gli2^tm1Alj	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:3614423
cx34	Gli2^tm1Alj/Gli2^tm1Alj Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3795856
cx35	Gli1^tm2Alj/Gli1^tm2Alj Gli2^tm1Alj/Gli2^tm1Alj	involves: 129/Sv * Black Swiss * Swiss Webster	MGI:3795854

Genotype
MGI:2176889

hm1

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: either: (involves: 129S1/Sv * 129X1/Sv) or (involves: 129S1/Sv * 129X1/Sv * CD-1)

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

mortality/aging

perinatal lethality, complete penetrance ( J:38381 )

• homozygotes are stillborn; resorbed embryos often found at late gestational stages

embryo

decreased embryo size ( J:38381 )

• visible at E10.5

growth/size/body

absent lower incisors ( J:38381 )

• 33% of animals are missing lower incisors

absent upper incisors ( J:38381 )

• 91% of animals lack upper incisors

absent maxillary shelf ( J:38381 )

• missing in severe cases of cleft palate

absent palatine bone horizontal plate ( J:38381 )

• missing in severe cases of cleft palate

abnormal palatal shelf fusion at midline ( J:38381 )

• in less severely affected embryos, the mutant shelves do elevate but show a delay in fusion

cleft secondary palate ( J:38381 )

• cleft palate is seen at birth with 64% penetrance

abnormal palatal shelf elevation ( J:38381 )

• in severely affected embryos, mutant palatal shelves were either do not elevate at all or only partially elevate

abnormal head shape ( J:38381 )

• at E14.5 head appears to be flattened

decreased embryo size ( J:38381 )

• visible at E10.5

microcephaly ( J:38381 )

• seen at E10.5

hearing/vestibular/ear

absent tympanic ring ( J:38381 )

• tympanic ring bones are missing in some homozygotes

homeostasis/metabolism

edema ( J:38381 )

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

craniofacial

abnormal basioccipital bone morphology ( J:38381 )

abnormal basisphenoid bone morphology ( J:38381 )

abnormal frontal bone morphology ( J:38381 )

• a deficiency of the medial portion of frontal and parietal bones is observed

abnormal parietal bone morphology ( J:38381 )

• a deficiency of the medial portion of frontal and parietal bones is observed

absent presphenoid bone ( J:38381 )

• in cases of severe cleft palate the presphenoid bone is absent

absent lower incisors ( J:38381 )

• 33% of animals are missing lower incisors

absent upper incisors ( J:38381 )

• 91% of animals lack upper incisors

small mandible ( J:38381 )

• lower jaw appears normal, but is reduced in size

absent maxillary shelf ( J:38381 )

• missing in severe cases of cleft palate

short maxilla ( J:38381 )

• truncation of distal maxilla is seen

absent palatine bone horizontal plate ( J:38381 )

• missing in severe cases of cleft palate

abnormal palatal shelf fusion at midline ( J:38381 )

• in less severely affected embryos, the mutant shelves do elevate but show a delay in fusion

cleft secondary palate ( J:38381 )

• cleft palate is seen at birth with 64% penetrance

abnormal palatal shelf elevation ( J:38381 )

• in severely affected embryos, mutant palatal shelves were either do not elevate at all or only partially elevate

abnormal head shape ( J:38381 )

• at E14.5 head appears to be flattened

skeleton

abnormal basioccipital bone morphology ( J:38381 )

abnormal basisphenoid bone morphology ( J:38381 )

abnormal frontal bone morphology ( J:38381 )

• a deficiency of the medial portion of frontal and parietal bones is observed

abnormal parietal bone morphology ( J:38381 )

• a deficiency of the medial portion of frontal and parietal bones is observed

absent presphenoid bone ( J:38381 )

• in cases of severe cleft palate the presphenoid bone is absent

absent lower incisors ( J:38381 )

• 33% of animals are missing lower incisors

absent upper incisors ( J:38381 )

• 91% of animals lack upper incisors

small mandible ( J:38381 )

• lower jaw appears normal, but is reduced in size

absent maxillary shelf ( J:38381 )

• missing in severe cases of cleft palate

short maxilla ( J:38381 )

• truncation of distal maxilla is seen

absent palatine bone horizontal plate ( J:38381 )

• missing in severe cases of cleft palate

abnormal long bone morphology ( J:38381 )

short humerus ( J:38381 )

bowed radius ( J:38381 )

short radius ( J:38381 )

short ulna ( J:38381 )

short femur ( J:38381 )

short fibula ( J:38381 )

short tibia ( J:38381 )

short sternum ( J:38381 )

• length of sternum is reduced

increased rib number ( J:38381 )

• bilateral pair of extra ribs are present in 36% and a unilateral extra rib occurs in 6%

absent intervertebral disk ( J:38381 )

• intervertebral disks are absent or reduced

abnormal spine curvature ( J:38381 )

• vertebral column often displayed a bend in the thoracic-lumbar region

abnormal vertebral body morphology ( J:38381 )

• ossification of vertebral bodies is reduced or absent

delayed bone ossification ( J:38381 )

• 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

short humerus ( J:38381 )

bowed radius ( J:38381 )

short radius ( J:38381 )

short ulna ( J:38381 )

short femur ( J:38381 )

short fibula ( J:38381 )

short tibia ( J:38381 )

short limbs ( J:38381 )

digestive/alimentary system

absent maxillary shelf ( J:38381 )

• missing in severe cases of cleft palate

absent palatine bone horizontal plate ( J:38381 )

• missing in severe cases of cleft palate

abnormal palatal shelf fusion at midline ( J:38381 )

• in less severely affected embryos, the mutant shelves do elevate but show a delay in fusion

cleft secondary palate ( J:38381 )

• cleft palate is seen at birth with 64% penetrance

abnormal palatal shelf elevation ( J:38381 )

• in severely affected embryos, mutant palatal shelves were either do not elevate at all or only partially elevate

Genotype
MGI:2676436

hm2

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal neuron differentiation ( J:112802 )

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

cellular

abnormal neuron differentiation ( J:112802 )

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

Genotype
MGI:4366500

hm3

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * FVB/N

skeleton

small mandibular condyloid process ( J:153743 )

• 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

absent temporomandibular joint disk ( J:153743 )

• 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

decreased chondrocyte number ( J:153743 )

• chondroprogenitor cells and prehypertrophic chondrocytes are reduced in number compared to in wild-type mice

abnormal epiphyseal plate morphology ( J:153743 )

• cells within the growth plate of the temporomandibular condyle are larger in size and disorganized compared to in wild-type mice

craniofacial

small mandibular condyloid process ( J:153743 )

• 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

absent temporomandibular joint disk ( J:153743 )

• 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

Genotype
MGI:2166993

hm4

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

respiratory system

abnormal lung development ( J:49603 )

• 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

decreased mesenchymal cell proliferation involved in lung development ( J:49603 )

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

small lung saccule ( J:49603 )

• at E18.5, mutant terminal air sacs are smaller and lined by thicker interstitial layers

thick lung-associated mesenchyme ( J:49603 )

• at E18.5, mutant interstitial mesenchymal cell layers are thicker than normal

increased type II pneumocyte number ( J:49603 )

• 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

small lung ( J:49603 )

• at E10.5 and E11.5, mutant lungs are significantly smaller than wild-type

decreased lung weight ( J:49603 )

• 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

pulmonary hypoplasia ( J:49603 )

• 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

abnormal right lung morphology ( J:49603 )

• at E10.5 and E11.5, a one-lobed right lung is observed, unlike the four-lobed right lung seen in wild-type embryos

abnormal tracheal cartilage morphology ( J:49603 )

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

trachea hypoplasia ( J:49603 )

• at E18.5, the mutant trachea is hypoplastic

trachea stenosis ( J:49603 )

• at E18.5

digestive/alimentary system

abnormal esophagus development ( J:49603 )

• the mutant esophagus fails to develop a smooth muscle layer

abnormal foregut morphology ( J:49603 )

• homozygotes display foregut malformations, including stenosis of the esophagus and trachea, lung hypoplasia and lung lobulation defects

abnormal esophageal smooth muscle morphology ( J:49603 )

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

esophagus stenosis ( J:49603 )

• at E18.5

esophagus hypoplasia ( J:49603 )

• 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

abnormal neural tube morphology ( J:152259 )

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

embryo

abnormal neural tube morphology ( J:152259 )

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

muscle

abnormal esophageal smooth muscle morphology ( J:49603 )

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

skeleton

abnormal tracheal cartilage morphology ( J:49603 )

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

cellular

decreased mesenchymal cell proliferation involved in lung development ( J:49603 )

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

Genotype
MGI:3665552

hm5

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

mortality/aging

perinatal lethality, complete penetrance ( J:94461 )

• lethality at birth is observed

nervous system

abnormal cerebellar foliation ( J:94461 )

• cerebellum has abnormal foliation that is more pronounced posteriorly; foliation is reduced

reduced cerebellar foliation ( J:94461 )

thin external granule cell layer ( J:94461 )

• 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

small cerebellum ( J:94461 )

• smaller than in wild-type

Genotype
MGI:4357968

ht6

• Allelic Composition: Gli2^tm1Alj/Gli2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

nervous system

abnormal neural tube morphology ( J:152259 )

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

embryo

abnormal neural tube morphology ( J:152259 )

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

Genotype
MGI:2173471

ht7

• Allelic Composition: Gli2^tm1Alj/Gli2^tm2.1Alj
• Genetic Background: either: (involves: 129) or (involves: 129 * Black Swiss)

nervous system

absent floor plate ( J:73074 )

• at E10.5 cells that express Shh and Foxa2 are absent

abnormal spinal cord morphology ( J:73074 )

• at E10.5 motor neurons occupy the ventral midline of the spinal cord

• the notochord is situated closer to the spinal cord

abnormal ventral interneuron 3 morphology ( J:73074 )

• decrease in the number of spinal cord V3 interneurons that are normally adjacent to the floor plate at E10.5

embryo

absent floor plate ( J:73074 )

• at E10.5 cells that express Shh and Foxa2 are absent

abnormal notochord morphology ( J:73074 )

• at E10.5 cells that express Shh and Foxa2 are absent

• the notochord is situated closer to the spinal cord

persistence of notochord tissue ( J:73074 )

• the notochord fails to regress

respiratory system

absent right lung accessory lobe ( J:73074 )

• the accessory lobe is absent

small lung ( J:73074 )

Genotype
MGI:4414941

ht8

• Allelic Composition: Gli2^tm5(GLI3)Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

embryo

abnormal neural tube morphology ( J:87948 )

• phenotype is similar to that of Gli2^tm1Alj mutant embryos, indicating that a low level of Gli3 is not enough to substitute for Gli2

absent floor plate ( J:87948 )

• absence of floor plate cells throughout the anterior/posterior (A/P) axis of the spinal cord

nervous system

abnormal neural tube morphology ( J:87948 )

• phenotype is similar to that of Gli2^tm1Alj mutant embryos, indicating that a low level of Gli3 is not enough to substitute for Gli2

absent floor plate ( J:87948 )

• absence of floor plate cells throughout the anterior/posterior (A/P) axis of the spinal cord

Genotype
MGI:3665554

ht9

• Allelic Composition: Gli2^tm1Alj/Gli2^tm6.1Alj
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL

mortality/aging

perinatal lethality, complete penetrance ( J:108507 )

• lethality at birth is observed

embryo

abnormal developmental patterning ( J:108507 )

• at E10.5, patterning of ventral spinal cord is abnormal

abnormal rostral-caudal axis patterning ( J:108507 )

• at E18.5, body axis is curved

nervous system

abnormal cerebellar foliation ( J:108507 )

• cerebellum has abnormal foliation that is more pronounced posteriorly; foliation is reduced

reduced cerebellar foliation ( J:108507 )

thin external granule cell layer ( J:108507 )

• 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

hydrocephaly ( J:108507 )

• seen in E18.5 embryos

small cerebellum ( J:108507 )

• smaller than in wild-type

Genotype
MGI:3665558

cn10

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Gli2^tm1Alj/Gli2^tm6Alj
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

growth/size/body

decreased body size ( J:108507 )

• adults are ~75% of size of wild-type littermates

behavior/neurological

tremors ( J:108507 )

• mice show deficits in motor control such as intention tremors consistent with cerebellar defects

impaired balance ( J:108507 )

• mutants have balance problems

abnormal gait ( J:108507 )

• mice have a wide-based gait

nervous system

nervous system phenotype ( J:108507 )

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

abnormal cerebellar lobule formation ( J:108507 )

• number of lobules in addition to cardinal lobes in vermis and hemispheres is greatly reduced compared to wild-type

abnormal cerebellum external granule cell layer morphology ( J:108507 )

• 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

thin external granule cell layer ( J:108507 )

• 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

abnormal cerebellar Purkinje cell layer ( J:108507 )

• 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

abnormal cerebellar granule layer morphology ( J:108507 )

• internal granule layer (IGL) is thinner compared to wild-type

abnormal cerebellar molecular layer ( J:108507 )

• dendritic arborization of PCs in molecular layer is less branched than normal

abnormal cerebellum vermis morphology ( J:108507 )

• central lobe is divided by a shallow fissure

abnormal cerebellum anterior vermis morphology ( J:108507 )

• fissure dividing anterobasal lobe is absent or shallow in most mutant brains

small cerebellum ( J:108507 )

• 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

Genotype
MGI:3665567

cn11

• Allelic Composition: En1^tm2(cre)Gld/En1⁺; Gli1^tm2Alj/Gli1^tm2Alj; Gli2^tm1Alj/Gli2^tm6Alj
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellum morphology ( J:108507 )

• cerebellum has decreased number of fissures compared to conditional Gli2 knockouts

abnormal cerebellum development ( J:108507 )

• only the five cardinal lobes of cerebellum can be discerned; other lobules do not form

abnormal cerebellar foliation ( J:108507 )

• decreased number of lobules (abnormal foliation) is observed

Genotype
MGI:3665562

cn12

• Allelic Composition: Gli2^tm1Alj/Gli2^tm6Alj; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL * Swiss Webster

nervous system

abnormal cerebellar foliation ( J:108507 )

• foliation occurs to a greater extent, with the vermis having a more defined intercrural structure and thicker IGL than in Gli2;En1 conditional knockouts

Genotype
MGI:4414944

cx13

• Allelic Composition: Gli1^tm2Alj/Gli1⁺; Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt/Gli3^Xt
• Genetic Background: involves: 101/H * 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster

nervous system

abnormal neuron differentiation ( J:87948 )

• progenitors for motor neurons, V1 and V2 interneurons are present but intermixed indicating abnormal spatial patterning

abnormal neuronal precursor proliferation ( J:87948 )

• increased proliferation of ventral spinal cord progenitors at E10.5

absent floor plate ( J:87948 )

• floor plate progenitors are missing

abnormal neuronal precursor cell number ( J:87948 )

• incorrect positioning and number of V0-V2 and motor neuron progenitors at E9.5

abnormal spinal cord morphology ( J:87948 )

• ventral spinal cord is expanded resulting in a wavy appearance

abnormal motor neuron morphology ( J:87948 )

• distribution of motor neurons varies at E12.5

decreased motor neuron number ( J:87948 )

• reduction in the number of differentiated motor neurons but an increase in their progenitors

abnormal ventral interneuron morphology ( J:87948 )

• absence of V3 progenitors and interneurons, however V0-V2 cells are formed

• fewer V2, V1, and V0 interneurons are seen in the hindlimb

abnormal ventral interneuron 3 morphology ( J:87948 )

• absence of V3 progenitors and interneurons, however V0-V2 cells are formed

embryo

absent floor plate ( J:87948 )

• floor plate progenitors are missing

cellular

abnormal neuron differentiation ( J:87948 )

• progenitors for motor neurons, V1 and V2 interneurons are present but intermixed indicating abnormal spatial patterning

abnormal neuronal precursor proliferation ( J:87948 )

• increased proliferation of ventral spinal cord progenitors at E10.5

Genotype
MGI:4414948

cx14

• Allelic Composition: Gli2^tm1Alj/Gli2⁺; Gli3^Xt/Gli3^Xt
• Genetic Background: involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster

nervous system

increased neuronal precursor cell number ( J:87948 )

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

Genotype
MGI:4414946

cx15

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt/Gli3⁺
• Genetic Background: involves: 101/H * 129S1/Sv * 129X1/SvJ * C3H/HeH * C57BL * CBA/H * Swiss Webster

nervous system

increased neuronal precursor cell number ( J:87948 )

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

Genotype
MGI:2676433

cx16

• Allelic Composition: Gli1^tm2Alj/Gli1^tm2Alj; Gli2^tm1Alj/Gli2⁺
• Genetic Background: involves: 129 * Black Swiss * Swiss Webster

embryo

abnormal floor plate morphology ( J:79392 )

• 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

persistence of notochord tissue ( J:79392 )

nervous system

abnormal floor plate morphology ( J:79392 )

• 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

small lung ( J:79392 )

Genotype
MGI:4357967

cx17

• Allelic Composition: Gli2^tm1Alj/Gli2⁺; Kif7^tm1.2Hui/Kif7^tm1.2Hui
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * CD-1

nervous system

abnormal neural tube morphology ( J:152259 )

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

embryo

abnormal neural tube morphology ( J:152259 )

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

Genotype
MGI:6113534

cx18

• Allelic Composition: Cdk20^tm1.1Jegg/Cdk20^tm1.1Jegg; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N

embryo

abnormal dorsal-ventral axis patterning ( J:243907 )

• more dramatic dorsalization of neural tube progenitor identity than in either single mutant

abnormal neural tube morphology ( J:243907 )

• more dramatic dorsalization of neural tube progenitor identity than in either single mutant

nervous system

abnormal neural tube morphology ( J:243907 )

• more dramatic dorsalization of neural tube progenitor identity than in either single mutant

Genotype
MGI:3664781

cx19

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Pax6^Sey/Pax6^Sey
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

abnormal neuron differentiation ( J:112802 )

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

cellular

abnormal neuron differentiation ( J:112802 )

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

Genotype
MGI:3795863

cx20

• Allelic Composition: Gli1^tm2Alj/Gli1⁺; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss * Swiss Webster

respiratory system

small lung ( J:79392 )

• at E12.5 lungs are smaller than in wild-type

Genotype
MGI:3614416

cx21

• Allelic Composition: Gli2^tm1Alj/Gli2⁺; Gli3^Xt-J/Gli3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1

limbs/digits/tail

polydactyly ( J:38381 )

• not different from Gli3 heterozygotes

Genotype
MGI:3614413

cx22

• Allelic Composition: Gli2^tm1Alj/Gli2⁺; Gli3^Xt-J/Gli3^Xt-J
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1

skeleton

abnormal skeleton morphology ( J:38381 )

• show an enhancement of the Gli3 null phenotype

polyphalangy ( J:38381 )

fusion of vertebral arches ( J:38381 )

• neural arches of other cervical vertebrae are fused in addition to the fusion of the C1 and C2 neural arches

limbs/digits/tail

polyphalangy ( J:38381 )

Genotype
MGI:2678685

cx23

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt-J/Gli3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1

craniofacial

mandible hypoplasia ( J:38381 )

• coronoid, condylar, angular and dental processes are hypoplastic

limbs/digits/tail

abnormal digit morphology ( J:38381 )

• on forelimbs, there is a postaxial stub of an extra digit

polydactyly ( J:38381 )

• display more severe preaxial polydactyly compared to Gli2 homozygotes

short humerus ( J:38381 )

• shortening of the humerus

short radius ( J:38381 )

• shortening of the radius; shortening is more severe than in the ulna

short ulna ( J:38381 )

• shortening of the ulna, although not as severe as the radius

short femur ( J:38381 )

short fibula ( J:38381 )

• not as severe as the tibia

short tibia ( J:38381 )

skeleton

abnormal skeleton morphology ( J:38381 )

• show an exacerbated phenotype in various skeletal elements with respect to Gli2 nulls

mandible hypoplasia ( J:38381 )

• coronoid, condylar, angular and dental processes are hypoplastic

abnormal long bone morphology ( J:38381 )

short humerus ( J:38381 )

• shortening of the humerus

short radius ( J:38381 )

• shortening of the radius; shortening is more severe than in the ulna

short ulna ( J:38381 )

• shortening of the ulna, although not as severe as the radius

short femur ( J:38381 )

short fibula ( J:38381 )

• not as severe as the tibia

short tibia ( J:38381 )

split sternum ( J:38381 )

• sternum is split rostrally and improperly segmented

abnormal vertebrae development ( J:38381 )

• there are severe abnormalities in chondrogenesis of ventral vertebral components

abnormal cartilage development ( J:38381 )

• there are severe abnormalities in chondrogenesis of ventral vertebral components

Genotype
MGI:2176890

cx24

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt-J/Gli3^Xt-J
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * CD-1

mortality/aging

embryonic lethality, complete penetrance ( J:38381 )

• double homozygotes die before E10.5

Genotype
MGI:4888267

cx25

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Ift122^sopb/Ift122^sopb
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J

embryo

abnormal neural tube morphology ( J:168317 )

• patterning resembles that in mice homozygous for Gli2^tm1Alj alone

nervous system

abnormal neural tube morphology ( J:168317 )

• patterning resembles that in mice homozygous for Gli2^tm1Alj alone

Genotype
MGI:3052545

cx26

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt-J/Gli3^Xt-J
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * Swiss Webster

nervous system

decreased motor neuron number ( J:92067 )

• 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

abnormal ventral interneuron morphology ( J:92067 )

• V1, V2a, and V2b interneurons expand down into the ventral midline becoming intermingled with one another and with motor neurons in embryos

abnormal ventral interneuron 0 morphology ( J:92067 )

• V0 interneurons are normal but increased in numbers in embryos

abnormal ventral interneuron 1 morphology ( J:92067 )

• V1 interneurons are also increased in numbers but only in the thoracic region of embryos

abnormal ventral interneuron 2 morphology ( J:92067 )

• V2 interneurons are reduced in number in embryos

abnormal ventral interneuron 3 morphology ( J:92067 )

• V3 interneurons absent in thoracic and lumbar spinal cord of embryos

Genotype
MGI:6489571

cx27

• Allelic Composition: Ankmy2^{tm1b(EUCOMM)Hmgu}/Ankmy2^{tm1b(EUCOMM)Hmgu}; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/6N

embryo

abnormal embryonic neuroepithelial layer differentiation ( J:297055 )

• limited ventralization of thoracic and lumbar level neural tube; extensive ventralization of cranial level neural tube

incomplete rostral neuropore closure ( J:297055 )

• open neural tube in hindbrain area at 26-28 somite stage (E9.5)

mortality/aging

embryonic lethality prior to organogenesis ( J:297055 )

• embryos are arrested at 26-28 somite stage (E9.5)

nervous system

abnormal embryonic neuroepithelial layer differentiation ( J:297055 )

• limited ventralization of thoracic and lumbar level neural tube; extensive ventralization of cranial level neural tube

incomplete rostral neuropore closure ( J:297055 )

• open neural tube in hindbrain area at 26-28 somite stage (E9.5)

exencephaly ( J:297055 )

• open neural tube in hindbrain area at 26-28 somite stage (E9.5)

Genotype
MGI:4355988

cx28

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Kif7^maki/Kif7^maki; Tg(Hlxb9-GFP)1Tmj/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

nervous system

abnormal neural tube morphology ( J:151965 )

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

absent floor plate ( J:151965 )

embryo

abnormal neural tube morphology ( J:151965 )

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

absent floor plate ( J:151965 )

Genotype
MGI:3579188

cx29

• Allelic Composition: Gli1^tm1Alj/Gli1^tm1Alj; Gli2^tm1Alj/Gli2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

neonatal lethality, incomplete penetrance ( J:60986 )

• most die shortly after birth with only 3.8% surviving to weaning age

embryo

abnormal floor plate morphology ( J:60986 )

• variable loss of cells expressing floor plate markers is seen in 2 of 5 mice in random patches in the posterior regions

abnormal notochord morphology ( J:60986 )

• at E12.5 and 14, notochord has not regressed from the ventral spinal cord

growth/size/body

decreased body size ( J:60986 )

• animals which survive to weaning are smaller

endocrine/exocrine glands

cryptorchism ( J:60986 )

♂

behavior/neurological

impaired righting response ( J:60986 )

• animals unable to right themselves

abnormal gait ( J:60986 )

• hopping gait

nervous system

abnormal floor plate morphology ( J:60986 )

• variable loss of cells expressing floor plate markers is seen in 2 of 5 mice in random patches in the posterior regions

abnormal motor neuron morphology ( J:60986 )

• motor neurons are located closer to the midline than normal

respiratory system

abnormal lung morphology ( J:60986 )

abnormal left lung morphology ( J:60986 )

• at E18.5, the left lobe is reduced in width

abnormal right lung accessory lobe morphology ( J:60986 )

• at E12.5, slight reduction in size of accessory lobe visible

• at E18.5, the accessory lobe is reduced in length and in width

abnormal right lung cranial lobe morphology ( J:60986 )

• at E18.5, the right cranial lobe is reduced in length

small lung ( J:60986 )

reproductive system

cryptorchism ( J:60986 )

♂

abnormal external male genitalia morphology ( J:60986 )

♂ • external genitalia are incompletely developed

digestive/alimentary system

abnormal digestive system morphology ( J:60986 )

• at 5-7 weeks of age the gut is distended

Genotype
MGI:3579187

cx30

• Allelic Composition: Gli1^tm1Alj/Gli1^tm1Alj; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

perinatal lethality, complete penetrance ( J:60986 )

• no double homozygotes survive past birth

lethality throughout fetal growth and development, incomplete penetrance ( J:60986 )

• fewer than expected double homozygotes are seen at E18.5

nervous system

absent pituitary gland ( J:60986 )

• at E12.5, pituitary gland is absent

abnormal telencephalon morphology ( J:60986 )

• dorsal and ventral regions of the telencephalon appeared abnormal

• neural epithelium is thickened in telencephalic region

abnormal motor neuron morphology ( J:60986 )

• motor neurons are induced in the ventral midline of the spinal cord, similar to Gli2 single homozygotes

endocrine/exocrine glands

absent pituitary gland ( J:60986 )

• at E12.5, pituitary gland is absent

respiratory system

abnormal lung morphology ( J:60986 )

• 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

small lung ( J:60986 )

limbs/digits/tail

abnormal digit morphology ( J:60986 )

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

Genotype
MGI:4936754

cx31

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt/Gli3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

respiratory system

tracheoesophageal fistula ( J:49603 )

• 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

abnormal lung morphology ( J:49603 )

• at E16.5, the left and right lobes are fused, resulting in a single-lobed lung

abnormal lung development ( J:49603 )

• 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 Gli2^tm1Alj mutant lungs have five and two lobes, respectively

abnormal lung bud morphology ( J:49603 )

• mutant lung buds do not form until E10.0, unlike in wild-type and homozygous Gli2^tm1Alj 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

pulmonary hypoplasia ( J:49603 )

• at E16.5, mutant lungs are more hypoplastic than those of wild-type or homozygous Gli2^tm1Alj mutant embryos

abnormal tracheal cartilage morphology ( J:49603 )

• at E16.5, the tracheal cartilaginous rings are more severely malformed than those in Gli2^tm1Alj mutant embryos

trachea stenosis ( J:49603 )

• at E16.5, tracheal stenosis is more severe than that in Gli2^tm1Alj mutant lungs

digestive/alimentary system

esophageal atresia ( J:49603 )

• at E11.5, mutant embryos display esophageal atresia with tracheoesophageal fistula

tracheoesophageal fistula ( J:49603 )

• 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

abnormal tracheal cartilage morphology ( J:49603 )

• at E16.5, the tracheal cartilaginous rings are more severely malformed than those in Gli2^tm1Alj mutant embryos

Genotype
MGI:4936829

cx32

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Gli3^Xt/Gli3^Xt
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:49603 )

• most double homozygous mutants die at ~E10.5

• a small number of double homozygous mutants survive to E13.5-E14.5

respiratory system

abnormal lung development ( J:49603 )

• no lung primordia are detected at E9.5 or later

absent lungs ( J:49603 )

• all double homozygous mutant mice lack lungs

abnormal trachea development ( J:49603 )

• no tracheal primordia are detected at E9.5 or later

absent trachea ( J:49603 )

• all double homozygous mutant mice lack a trachea

digestive/alimentary system

abnormal esophagus development ( J:49603 )

• no esophageal primordia are detected at E9.5 or later

abnormal foregut morphology ( J:49603 )

• 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

absent esophagus ( J:49603 )

• all double homozygous mutant mice lack an esophagus

embryo

abnormal endoderm development ( J:49603 )

• the foregut endoderm fails to develop into lung, trachea and esophagus

• however, hepatic and pancreatic buds are present

Genotype
MGI:3614423

cx33

• Allelic Composition: Gli1^tm1Alj/Gli1⁺; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

respiratory system

abnormal lung morphology ( J:60986 )

• at E12.5 and E18.5, lungs appear to have 2 small lobes

small lung ( J:60986 )

• at E12.5 and E18.5, lungs appear smaller than normal

Genotype
MGI:3795856

cx34

• Allelic Composition: Gli2^tm1Alj/Gli2^tm1Alj; Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:79392 )

• some embryos survive to E10.5; at E11.5, no embryos are recovered

nervous system

nervous system phenotype ( J:79392 )

N

abnormal brain development ( J:79392 )

• at E10.5 dorsal brain has not closed

exencephaly ( J:79392 )

• embryos found at E10.5 exhibit exencephaly

abnormal spinal cord morphology ( J:79392 )

• only small number of V3 interneurons remain in ventral midline of spinal cord at E9.5

increased motor neuron number ( J:79392 )

• more motor neurons are generated than in Gli2-null mutants; motor neuron population expands into dorsal half of spinal cord

abnormal ventral interneuron 3 morphology ( J:79392 )

• number of V3 interneurons is reduced compared to Ptc-null embryos at E9.5

Genotype
MGI:3795854

cx35

• Allelic Composition: Gli1^tm2Alj/Gli1^tm2Alj; Gli2^tm1Alj/Gli2^tm1Alj
• Genetic Background: involves: 129/Sv * Black Swiss * Swiss Webster

respiratory system

impaired lung lobe morphogenesis ( J:79392 )

• lungs have only 2 lobes at E12.5

small lung ( J:79392 )

• at E12.5 and E18.5, lungs are smaller than in Gli2^tm1Alj homozygotes and much smaller than wild-type

limbs/digits/tail

polydactyly ( J:79392 )

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