Phenotypes associated with this allele

• Allele Symbol: Shh⁺
• Allele Name: wild type
• Allele ID: MGI:2432096
• Summary: 63 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Shh^Dsh/Shh^+	B10Rl.Cg-Shh^Dsh	MGI:3583764
ht2	Shh^tm1b(EUCOMM)Wtsi/Shh^+	C57BL/6N-Shh^tm1b(EUCOMM)Wtsi/H	MGI:5757706
ht3	Shh^Dsh/Shh^+	involves: 101 * C3H * C57BL * SEC	MGI:3583762
cn4	Shh^tm1(EGFP/cre)Cjt/Shh^+ Sox9^tm2Crm/Sox9^tm2Crm	B6.Cg-Shh^tm1(EGFP/cre)Cjt Sox9^tm2Crm	MGI:6378814
cn5	Dicer1^tm1Bdh/Dicer1^tm1Bdh Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129	MGI:4943703
cn6	Robo1^tm1Matl/Robo1^tm1Matl Robo2^tm1Rilm/Robo2^tm1Rilm Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129	MGI:5522668
cn7	Dicer1^tm1Bdh/Dicer1^+ Yy1^tm2.1Yshi/Yy1^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129 * 129S4/SvJae * C57BL/6	MGI:5902326
cn8	Dicer1^tm1Mmk/Dicer1^tm1Mmk Fgf9^tm1.1Fwan/Fgf9^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129 * 129S4/SvJaeSor * C57BL/6J	MGI:5751752
cn9	Dicer1^tm1Mmk/Dicer1^tm1Mmk Fgf9^tm1.1Fwan/Fgf9^tm1.1Fwan Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129 * 129S4/SvJaeSor * C57BL/6J	MGI:5751753
cn10	Dicer1^tm1Mmk/Dicer1^tm1Mmk Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129 * C57BL/6J	MGI:5751748
cn11	Ift88^tm1Bky/Ift88^tm1Bky Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129P2/OlaHsd	MGI:6378813
cn12	Sox9^tm1Gsr/Sox9^tm1Gsr Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129P2/OlaHsd	MGI:5557988
cn13	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac	MGI:5298088
cn14	Rbpj^tm1Hon/Rbpj^tm1.1Hon Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:4948663
cn15	Gt(ROSA)26Sor^tm1(tetO-Sox9)Msan/Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5557985
cn16	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Gt(ROSA)26Sor^tm1(Fgf8)Lma/Gt(ROSA)26Sor^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5694211
cn17	Fgfr1^tm1Jpa/Fgfr1^tm1Jpa Fgfr2^tm1Dor/Fgfr2^tm1Dor Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5694226
cn18	Sp8^tm1Smb/Sp8^tm1Smb Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:7437679
cn19	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:4361162
cn20	Foxp4^tm2.1Eem/Foxp4^tm2.1Eem Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5433105
cn21	Foxp1^tm1.1Pwt/Foxp1^tm1.1Pwt Foxp4^tm2.1Eem/Foxp4^tm2.1Eem Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5433106
cn22	Disp1^tm1Pab/Disp1^tm1Pab Shh^tm2Chg/Shh^+ Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3687546
cn23	Shh^tm2Chg/Shh^+ Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3687544
cn24	Chd7^tm1.1Dmm/Chd7^tm1.1Dmm Gt(ROSA)26Sor^tm6(CAG-ZsGreen1)Hze/Gt(ROSA)26Sor^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S1/SvlmJ * 129S6/SvEvTac * C57BL/6J * SJL/J	MGI:7518701
cn25	E2f4^tm2.1Lees/E2f4^tm2.1Lees Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6	MGI:5904347
cn26	Kras^tm4Tyj/Kras^+ Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:5298087
cn27	Yy1^tm2.1Yshi/Yy1^tm2.1Yshi Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S4/SvJae * C57BL/6J	MGI:5902322
cn28	Gt(ROSA)26Sor^tm1(Notch1)Dam/Gt(ROSA)26Sor^+ Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129S4/SvJaeSor * 129S6/SvEvTac	MGI:3718107
cn29	Fgfr1^tm3.2Cxd/Fgfr1^tm3.2Cxd Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S6/SvEvTac	MGI:3606229
cn30	Fgfr1^tm3.1Cxd/Fgfr1^tm3.2Cxd Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S6/SvEvTac	MGI:3607119
cn31	Gt(ROSA)26Sor^tm1(Fgf8)Lma/Gt(ROSA)26Sor^+ Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129S6/SvEvTac	MGI:5694209
cn32	Gt(ROSA)26Sor^tm1(Smo/EYFP)Amc/Gt(ROSA)26Sor^tm1(Smo/EYFP)Amc Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:3810321
cn33	Ar^tm2Ska/Y Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:4461253
cn34	Wnt1^tm1.1Mze/Wnt1^tm1.1Mze Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129S6/SvEvTac * C57BL/6N	MGI:5495282
cn35	Pofut1^tm2Pst/Pofut1^tm1Pst Shh^tm2(cre/ERT2)Cjt/Shh^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL	MGI:4948658
cn36	Disp1^icb/Disp1^tm2Amc Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129/Sv * C57BL/6J * SWR	MGI:3513048
cn37	Disp1^tm2.1Amc/Disp1^tm2Amc Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129/Sv * C57BL/6J * SWR	MGI:3513044
cn38	Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129X1/SvJ	MGI:5544581
cn39	Disp1^icb/Disp1^tm1Amc Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: 129X1/SvJ * C57BL/6J	MGI:3054017
cn40	Gt(ROSA)26Sor^tm4(CAG-lacZ,-EGFP)Dym/Gt(ROSA)26Sor^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	involves: C57BL/6	MGI:3777639
cn41	Gt(ROSA)26Sor^tm2(Sp8)Lma/Gt(ROSA)26Sor^+ Shh^tm1(EGFP/cre)Cjt/Shh^+	Not Specified	MGI:5694220
cx42	Ccd/Ccd^+ Shh^Dsh/Shh^+	involves: 101 * C3H * C57BL * C57BL/10Rl * SEC	MGI:3583774
cx43	Rr29^tm1.1Bobh/Rr29^+ Shh^tm1Chg/Shh^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5613161
cx44	Shh^tm1Chg/Shh^+ Sulf1^Gt(XM190)Byg/Sulf1^Gt(XM190)Byg Sulf2^Gt(PST111)Byg/Sulf2^Gt(PST111)Byg	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10	MGI:3812210
cx45	Nr5a1^tm1.1Hain/Nr5a1^tm1.1Hain Shh^tm1Amc/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5292679
cx46	Hhat^Tg(TFAP2A-cre)1Will/Hhat^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5447986
cx47	Rr26^tm1Svok/Rr26^tm1Svok Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5562302
cx48	Shh^+/Shh^tm1Chg Zic2^Ku/Zic2^+	involves: 129S1/Sv * 129X1/SvJ * BALB/cAnNCrl * C3H/HeH	MGI:5827502
cx49	Shh^tm1Chg/Shh^+ Vps25^m1Lis/Vps25^m1Lis	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J	MGI:5751502
cx50	Ndst1^tm1.1Grob/Ndst1^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3589447
cx51	Ndst1^tm1.1Grob/Ndst1^tm1.1Grob Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3589448
cx52	Six3^tm3.1Gco/Six3^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3814907
cx53	Gas1^tm1Fan/Gas1^tm1Fan Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7386875
cx54	Rr45^tm1.1Tshir/Rr45^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/JNCrlj	MGI:6144003
cx55	Rr117^tm1.1Dje/Rr117^+ Shh^tm1Amc/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N	MGI:4948512
cx56	Gas1^tm2Fan/Gas1^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3711885
cx57	Gas1^tm2Fan/Gas1^tm2Fan Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3711884
cx58	Rr115^em1Bobh/Rr115^+ Shh^tm1Chg/Shh^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:7367584
cx59	Shh^tm1Chg/Shh^+ Tg(Shh)#Dje/0	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3665550
cx60	Shh^tm1(EGFP/cre)Cjt/Shh^+ Sox17^tm1Ysk/Sox17^+	involves: 129S1/Sv * C57BL/6	MGI:6113949
cx61	Gas1^tm2Fan/Gas1^tm2Fan Shh^tm1Chg/Shh^+	involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3711877
cx62	Disp1^tm2.1Amc/Disp1^tm2.1Amc Shh^tm1Amc/Shh^+	involves: 129/Sv * C57BL/6J * SWR	MGI:3513050
cx63	Disp1^icb/Disp1^tm1Amc Shh^tm1Amc/Shh^+	involves: 129X1/SvJ * C57BL/6J	MGI:3052728

Genotype
MGI:3583764

ht1

• Allelic Composition: Shh^Dsh/Shh⁺
• Genetic Background: B10Rl.Cg-Shh^Dsh

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

cellular

decreased chondrocyte proliferation ( J:97323 )

• proliferation is reduced in nondifferentiating chondocytes and no proliferation of chondrocytes is seen where joints form

skeleton

decreased chondrocyte proliferation ( J:97323 )

• proliferation is reduced in nondifferentiating chondocytes and no proliferation of chondrocytes is seen where joints form

abnormal cranium morphology ( J:16170 )

abnormal neurocranium morphology ( J:16170 )

• have one or two holes between the frontal bones and 4 of 30 exhibit frontal-perietal bone fusion

• have one or more extra bones subdivided off between middle of parietals and interparietal bone

abnormal frontal bone morphology ( J:14105 , J:16170 )

• have a large hole between the frontals (J:14105)

• frontals fuse behind the hole (that is between the frontal bones) and the fusion complex extends halfway or more between the parietals toward the interparietal bone and the frontals bulge upward (J:16170)

thin interparietal bone ( J:16170 )

• width of the interparietal bone is decreased by 2%

occipital bone foramen ( J:16170 )

• occipital foramen with peculiar wide indentation on the dorsal side

abnormal maxilla morphology ( J:16170 )

• have large stalactite bones on maxilla

abnormal phalanx morphology ( J:14105 , J:97323 )

• one phalanx is absent in each digit that is shortened and phalanges have an abnormal shape and abnormal joints between them (J:14105)

brachyphalangia ( J:14105 , J:97323 )

• at least one of the phalanges remaining is short and phalanges on digit 1 are shortened (J:14105)

short metacarpal bones ( J:97323 )

• at 4 weeks of age, metacarpals are mildy shortened

abnormal rib morphology ( J:14105 , J:16170 )

• have bony plates over many ventral ribs (J:14105)

• have bony plates over many ventral ribs (J:16170)

abnormal vertebrae morphology ( J:16170 )

• dorsal dyssymphysis of the 9 most anterior vertebrae

abnormal cartilage morphology ( J:97323 )

abnormal cartilage development ( J:97323 )

• beginning at E14.5, chondrogenesis is delayed in the phalanges and metacarpals/tarsals

abnormal chondrocyte differentiation ( J:97323 )

• in the proximal and middle phalanges, chondrocytes remain undifferentiated, do not align in columns and do not hypertrophy

abnormal joint morphology ( J:97323 )

• joint cavitation is disturbed and joint formation is delayed or absent in the digits

fused joints ( J:97323 )

• the metacarpophalangeal joint is fused in digit IV

cervical vertebral fusion ( J:14105 )

• dyssymphyses of many cervical vertebrae

fusion of atlas and odontoid process ( J:16170 )

• the odontoid peg is not connected to the axis but fuses to the ventral inside of the atlas

limbs/digits/tail

abnormal phalanx morphology ( J:14105 , J:97323 )

• one phalanx is absent in each digit that is shortened and phalanges have an abnormal shape and abnormal joints between them (J:14105)

brachyphalangia ( J:14105 , J:97323 )

• at least one of the phalanges remaining is short and phalanges on digit 1 are shortened (J:14105)

brachydactyly ( J:14105 , J:16170 , J:97323 )

• digits 2-5 are short on all four extremities (J:14105)

syndactyly ( J:14105 , J:16170 , J:97323 )

• metatarsal-phalanx 1 fusion on digit 4 (J:14105)

• 15 of 30 have metatarsal-phalanx 1 fusion on digit 4 and 4 of 30 have metacarpal-phalanx 1 fusion on digit 4 (J:16170)

• fusion of the first and second phalanges of digits II-V (J:97323)

abnormal hindlimb morphology ( J:16170 )

• bony deposits in tissue behind calcaneus

short metacarpal bones ( J:97323 )

• at 4 weeks of age, metacarpals are mildy shortened

craniofacial

abnormal cranium morphology ( J:16170 )

abnormal neurocranium morphology ( J:16170 )

• have one or two holes between the frontal bones and 4 of 30 exhibit frontal-perietal bone fusion

• have one or more extra bones subdivided off between middle of parietals and interparietal bone

abnormal frontal bone morphology ( J:14105 , J:16170 )

• have a large hole between the frontals (J:14105)

• frontals fuse behind the hole (that is between the frontal bones) and the fusion complex extends halfway or more between the parietals toward the interparietal bone and the frontals bulge upward (J:16170)

thin interparietal bone ( J:16170 )

• width of the interparietal bone is decreased by 2%

occipital bone foramen ( J:16170 )

• occipital foramen with peculiar wide indentation on the dorsal side

abnormal maxilla morphology ( J:16170 )

• have large stalactite bones on maxilla

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
brachydactyly type A1		DOID:0110964	OMIM:112500	J:97323

Genotype
MGI:5757706

ht2

• Allelic Composition: Shh^{tm1b(EUCOMM)Wtsi}/Shh⁺
• Genetic Background: C57BL/6N-Shh^{tm1b(EUCOMM)Wtsi}/H
• Cell Lines: EPD0339_3_A12

Data Sources

IMPC Data for Shh

adipose tissue

increased total body fat amount ( J:211773 )

♂

IMPC - HAR

growth/size/body

decreased lean body mass ( J:211773 )

♂

IMPC - HAR

homeostasis/metabolism

increased circulating HDL cholesterol level ( J:211773 )

♀

IMPC - HAR

impaired glucose tolerance ( J:211773 )

♂

IMPC - HAR

skeleton

decreased bone mineral content ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:3583762

ht3

• Allelic Composition: Shh^Dsh/Shh⁺
• Genetic Background: involves: 101 * C3H * C57BL * SEC

limbs/digits/tail

brachydactyly ( J:14105 )

Genotype
MGI:6378814

cn4

• Allelic Composition: Shh^{tm1(EGFP/cre)Cjt}/Shh⁺; Sox9^tm2Crm/Sox9^tm2Crm
• Genetic Background: B6.Cg-Shh^{tm1(EGFP/cre)Cjt} Sox9^tm2Crm

embryo

abnormal primitive urogenital sinus morphology ( J:281428 )

• prostatic bud initiation from the urogenital sinus epithelium is unaffected, but buds fail to elongate

Genotype
MGI:4943703

cn5

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129

mortality/aging

perinatal lethality, complete penetrance ( J:106072 )

• mice die at birth

respiratory system

abnormal lung development ( J:106072 )

• at E12.5, fewer branches are observed and the distal tips of the newly formed branches appear dilated

• the number of dilated branching tips observed at E12.5 corresponds to the number of large, fluid-filled sacs seen at E15.5

• defective branching morphogenesis occurs prior to the increased cell death seen in the distal epithelium at E13.0

• at E11.75, expression of Fgf10 (a key gene involved in lung development) is already up-regulated and expanded in the mesenchyme of mutant lungs

abnormal lung epithelium morphology ( J:106072 )

• at E15.5, mutant lung epithelial cells form large, fluid-filled sacs within each lobe, indicating a severe branching defect

• at E15.5, the mutant epithelium is often detached from the mesenchyme, unlike in control lungs

• at E12.25, increased epithelial cell death is ectopically observed in the secondary bronchi of mutant lungs in addition to the normal pattern of cell death seen in the trachea and primary bronchi

• at E12.5 and E12.75, intense epithelial cell death is prolonged in the mutant trachea and bronchi, unlike in control and wild type lungs

• by E13.0, aberrant cell death is observed in the entire mutant lung epithelium, including the distal branching region, but not in the mesenchyme

small lung lobe ( J:106072 )

• after E13.5, each mutant lung lobe is proportionally smaller than that in control lungs

• however, each lobe maintains a normal shape, indicating a normal lobation pattern

Genotype
MGI:5522668

cn6

• Allelic Composition: Robo1^tm1Matl/Robo1^tm1Matl; Robo2^tm1Rilm/Robo2^tm1Rilm; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129

normal phenotype

no abnormal phenotype detected ( J:193400 )

• normal organ position, diaphragm formation and lung inflation

Genotype
MGI:5902326

cn7

• Allelic Composition: Dicer1^tm1Bdh/Dicer1⁺; Yy1^tm2.1Yshi/Yy1⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6

respiratory system

respiratory system phenotype ( J:239777 )

N • embryos do not present lung defects

Genotype
MGI:5751752

cn8

• Allelic Composition: Dicer1^tm1Mmk/Dicer1^tm1Mmk; Fgf9^tm1.1Fwan/Fgf9⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6J

respiratory system

respiratory system phenotype ( J:224791 )

N • mice show rescue of the lung phenotypes seen in single conditional Dicer1 mutants, showing smaller lungs, reduced epithelial dilation, mesenchymal thickness and mesenchymal proliferation

Genotype
MGI:5751753

cn9

• Allelic Composition: Dicer1^tm1Mmk/Dicer1^tm1Mmk; Fgf9^tm1.1Fwan/Fgf9^tm1.1Fwan; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6J

respiratory system

respiratory system phenotype ( J:224791 )

N • mice show rescue of the lung phenotypes seen in single conditional Dicer1 mutants, showing smaller lungs with reduced cystic dilation of epithelial ducts

Genotype
MGI:5751748

cn10

• Allelic Composition: Dicer1^tm1Mmk/Dicer1^tm1Mmk; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129 * C57BL/6J

respiratory system

increased mesenchymal cell proliferation involved in lung development ( J:224791 )

• E12.5 lungs show increased mesenchymal proliferation

lung cyst ( J:224791 )

• E14.5 and E16.5 lungs show cystic expansion of the epithelial ducts

enlarged lung ( J:224791 )

• lungs are larger at E12.5 but are similar in size to controls at E14.5 and E16.5

abnormal branching involved in lung morphogenesis ( J:224791 )

• E12.5, E14.5, and E16.5 lungs exhibit reduced branching

abnormal lung-associated mesenchyme development ( J:224791 )

• E12.5 lungs exhibit expanded mesenchyme

abnormal lung epithelium morphology ( J:224791 )

• E12.5 lungs exhibit dilated epithelial ducts

• E14.5 and E16.5 lungs show cystic expansion of the epithelial ducts

cellular

increased mesenchymal cell proliferation involved in lung development ( J:224791 )

• E12.5 lungs show increased mesenchymal proliferation

growth/size/body

lung cyst ( J:224791 )

• E14.5 and E16.5 lungs show cystic expansion of the epithelial ducts

enlarged lung ( J:224791 )

• lungs are larger at E12.5 but are similar in size to controls at E14.5 and E16.5

Genotype
MGI:6378813

cn11

• Allelic Composition: Ift88^tm1Bky/Ift88^tm1Bky; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129P2/OlaHsd

craniofacial

abnormal palatal rugae morphology ( J:281425 )

• variable penetrance of highly disorganized palatal rugae. including waved, folded, supernumerary, absence, shortened and fragmented palatal rugae, observed in the intermolar rugae

• no obvious anomalies were found in the antemolar rugae

digestive/alimentary system

abnormal palatal rugae morphology ( J:281425 )

• variable penetrance of highly disorganized palatal rugae. including waved, folded, supernumerary, absence, shortened and fragmented palatal rugae, observed in the intermolar rugae

• no obvious anomalies were found in the antemolar rugae

growth/size/body

abnormal palatal rugae morphology ( J:281425 )

• variable penetrance of highly disorganized palatal rugae. including waved, folded, supernumerary, absence, shortened and fragmented palatal rugae, observed in the intermolar rugae

• no obvious anomalies were found in the antemolar rugae

Genotype
MGI:5557988

cn12

• Allelic Composition: Sox9^tm1Gsr/Sox9^tm1Gsr; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

perinatal lethality, incomplete penetrance ( J:202984 )

• 1 of 3 pups died at birth

postnatal lethality, complete penetrance ( J:202984 )

• the 2 pups that survived past birth had to be euthanized by P7

respiratory system

lung cyst ( J:202984 )

• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips

abnormal branching involved in lung morphogenesis ( J:202984 )

• cultured lungs from E12.5 embryos show a significant reduction in branching

• branch tips are larger and rounder and lead to large open spaces in the lung

• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium

abnormal lung epithelium morphology ( J:202984 )

• distal epithelial tips show a range of defects including absence of microvilli, apical membranous blebs and disrupted cell-cell adhesion

• the basal epithelial surface is not uniform and many cells have a rounded appearance with membranous blebs projecting into the subcellular space

• the extracellular matrix and stabilized tubulin appear disrupted at the basal surfaces

small lung ( J:202984 )

• noticeable by E14.5 and more significant by E16.5

respiratory distress ( J:202984 )

• pups that survive birth have difficulty breathing

cellular

abnormal cell differentiation ( J:202984 )

• apparent precocious differentiation of distal tip progenitor cells into type 2 alveolar cells at E14.5

decreased cell migration ( J:202984 )

• migration of epithelial cells from cultured E12.5 lung buds is decreased compared to controls

decreased cell proliferation ( J:202984 )

• significant decrease in total lung epithelial cell proliferation at E14.5 resulting from a decrease in proliferation of the distal tip epithelium

growth/size/body

lung cyst ( J:202984 )

• develop large, cyst-like structures at the distal epithelial branch tips that are the result of larger, rounder branch tips

Genotype
MGI:5298088

cn13

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac

integument

integument phenotype ( J:172048 )

N • no macroscopic or microscopic skin tumors are observed up to 4 months after tamoxifen treatment

Genotype
MGI:4948663

cn14

• Allelic Composition: Rbpj^tm1Hon/Rbpj^tm1.1Hon; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

respiratory system

abnormal respiratory epithelium morphology ( J:150051 )

• at E18.5, the respiratory epithelium was populated almost exclusively by Foxj1-expressing ciliated cells, unlike in control lungs where ciliated cells were interspersed with secretory Clara cells

• at E18.5, Ki67 labeling was dramatically reduced in large, medium and small airways, suggesting a severe decrease in epithelial cell proliferation relative to control lungs

• however, goblet cell fate was not lost, as shown by PAS and Alcian Blue staining of tracheal sections at birth (P0)

absent club cells ( J:150051 )

• no secretory Clara cells were detected at E18.5, as determined by specific marker analysis

Genotype
MGI:5557985

cn15

• Allelic Composition: Gt(ROSA)26Sor^{tm1(tetO-Sox9)Msan}/Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

respiratory system

abnormal lung morphology ( J:202984 )

• decrease in airway spaces at E18.5

lung cyst ( J:202984 )

• develop large, cyst-like structures at the distal epithelial branch tips

• cystic buds appear to collapse by E18.5

small lung ( J:202984 )

• noticeable by E14.5 and more significant by E16.5

growth/size/body

lung cyst ( J:202984 )

• develop large, cyst-like structures at the distal epithelial branch tips

• cystic buds appear to collapse by E18.5

Genotype
MGI:5694211

cn16

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Gt(ROSA)26Sor^tm1(Fgf8)Lma/Gt(ROSA)26Sor⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:223057 )

N • a cone-shaped tubercle structure is discernable unlike in urethral epithelium knock-out of beta-catenin

abnormal reproductive system development ( J:223057 )

• mice exhibit failed cloaca septation

limbs/digits/tail

abnormal tail development ( J:223057 )

Genotype
MGI:5694226

cn17

• Allelic Composition: Fgfr1^tm1Jpa/Fgfr1^tm1Jpa; Fgfr2^tm1Dor/Fgfr2^tm1Dor; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

reproductive system phenotype ( J:223057 )

N • mice exhibit normal early growth, size and shape of genital tubercles

renal/urinary system

abnormal urethra urothelium morphology ( J:223057 )

• abnormal maturation of urethral epithelium

Genotype
MGI:7437679

cn18

• Allelic Composition: Sp8^tm1Smb/Sp8^tm1Smb; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

craniofacial phenotype ( J:200761 )

N • mice show partial craniofacial rescue of anterior structures; the medial facial prominences partially merge with the lateral and maxillary prominences to form an identifiable snout by E18.5

abnormal craniofacial development ( J:200761 )

• despite partial rescue of anterior structures, the more dorsal structures of the skull and forehead are not rescued

vision/eye

ocular hypertelorism ( J:200761 )

• mice display an inner canthal distance of 5.33 mm +/- 0.26 mm relative to 4.4 mm +/- 0.09 mm for wild-type controls and 6.1 mm +/- 0.45 mm for Sp8^tm1Smb homozygotes with two wild-type Shh alleles, indicating partial rescue of the hypertelorism phenotype

Genotype
MGI:4361162

cn19

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

respiratory system

abnormal lung development ( J:153098 )

• mice exhibit an expansion of lung endoderm progenitor cells into the stomach unlike in wild-type mice

absent lung buds ( J:153098 )

• mice lack tracheal budding

absent lungs ( J:153098 )

• mice lack lung specification

Genotype
MGI:5433105

cn20

• Allelic Composition: Foxp4^tm2.1Eem/Foxp4^tm2.1Eem; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

mortality/aging ( J:185603 )

N • mice exhibit normal prenatal and postnatal survival

Genotype
MGI:5433106

cn21

• Allelic Composition: Foxp1^tm1.1Pwt/Foxp1^tm1.1Pwt; Foxp4^tm2.1Eem/Foxp4^tm2.1Eem; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:185603 )

• mice die within minutes of birth of apparent respiratory distress

respiratory system

decreased club cell number ( J:185603 )

• in the proximal airways at E18.5

abnormal respiratory system development ( J:185603 )

• as determined by marker expression, mice exhibit an increase in ciliated epithelial cell differentiation compared with control mice

respiratory distress ( J:185603 )

• at birth

Genotype
MGI:3687546

cn22

• Allelic Composition: Disp1^tm1Pab/Disp1^tm1Pab; Shh^tm2Chg/Shh⁺; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

perinatal lethality, complete penetrance ( J:109101 )

• survive to at least E18.5

limbs/digits/tail

abnormal digit morphology ( J:109101 )

• digits show segmentation and calcification defects

preaxial polydactyly ( J:109101 )

• develop 6-7 digits per limb (preaxial polydactyly)

Genotype
MGI:3687544

cn23

• Allelic Composition: Shh^tm2Chg/Shh⁺; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

mortality/aging

perinatal lethality, complete penetrance ( J:125109 )

• animals die perinatally

nervous system

holoprosencephaly ( J:125109 )

• brain defects mimic human holoprosencephaly but external craniofacial morphology is relatively unaffected

increased forebrain size ( J:125109 )

• enlarged

increased midbrain size ( J:125109 )

• enlarged midbrain

enlarged brain ventricles ( J:125109 )

• ventricles are enlarged at E10.5

abnormal choroid plexus morphology ( J:125109 )

• development is defective at E13.5

abnormal telencephalon morphology ( J:125109 )

• telencephalic ventricles are widely separated at E10.5

• at E12.5, telencephalon lacks thickened hippocampal neuroepithelium

• at E10.5 dorsal midline has failed to invaginate in contrast to wild-type

abnormal hippocampus development ( J:125109 )

• defective at E13.5

abnormal telencephalon development ( J:125109 )

• apoptotic activity is eliminated in dorsal midline of telencephalon in contrast to wild-type at E9.5; apoptosis is 7-fold lower than in wild-type

• at E10, proliferation in roof plate region is similar to adjacent tissues and higher than seen in wild-type whereas proliferation is differentially reduced in wild-type embryo roof plate region

• dorsal midline is severely hypoplastic and lacks conjunction of corpus callosum and septum

• increased proliferation and decreased apoptosis persists at E10.5

• telencephalon lacks middle anterior commissure and characteristic choroid plexuses and hippocampal structures that are seen in wild-type; telencephalon lacks well-formed U-shaped hippocampus and ventricles are separated by enlarged thalamus

abnormal corpus callosum morphology ( J:125109 )

• frequent agenesis of dorsal corpus callosum is seen

absent olfactory bulb ( J:125109 )

• mutants lack olfactory bulbs

abnormal embryonic/fetal subventricular zone morphology ( J:125109 )

• a third eminence in addition to LGE and MGE is observed in mutants at E12.5

abnormal lateral ganglionic eminence morphology ( J:125109 )

• eminence is expanded at expense of cortical domain of telencephalon

abnormal medial ganglionic eminence morphology ( J:125109 )

• eminence is expanded at expense of cortical domain of telencephalon

craniofacial

abnormal neurocranium morphology ( J:125109 )

• many embryos display bulging cranium

abnormal maxillary shelf morphology ( J:125109 )

• the maxillary shelves are not fully mineralized in the mutant

palatal shelves fail to meet at midline ( J:125109 )

• palatal shelves fail to fuse; at E15.5, skeletal staining further shows the presence of widely separated palatal shelves

cleft secondary palate ( J:125109 )

• mutants have cleft secondary palate

digestive/alimentary system

abnormal maxillary shelf morphology ( J:125109 )

• the maxillary shelves are not fully mineralized in the mutant

palatal shelves fail to meet at midline ( J:125109 )

• palatal shelves fail to fuse; at E15.5, skeletal staining further shows the presence of widely separated palatal shelves

cleft secondary palate ( J:125109 )

• mutants have cleft secondary palate

skeleton

abnormal neurocranium morphology ( J:125109 )

• many embryos display bulging cranium

abnormal maxillary shelf morphology ( J:125109 )

• the maxillary shelves are not fully mineralized in the mutant

limbs/digits/tail

polydactyly ( J:109101 )

• develop six to seven digits per limb with complete formation of digits 2-5 (preaxial polydactyly)

growth/size/body

abnormal maxillary shelf morphology ( J:125109 )

• the maxillary shelves are not fully mineralized in the mutant

palatal shelves fail to meet at midline ( J:125109 )

• palatal shelves fail to fuse; at E15.5, skeletal staining further shows the presence of widely separated palatal shelves

cleft secondary palate ( J:125109 )

• mutants have cleft secondary palate

Genotype
MGI:7518701

cn24

• Allelic Composition: Chd7^tm1.1Dmm/Chd7^tm1.1Dmm; Gt(ROSA)26Sor^{tm6(CAG-ZsGreen1)Hze}/Gt(ROSA)26Sor⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S1/SvlmJ * 129S6/SvEvTac * C57BL/6J * SJL/J

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:310063 )

N • normal hair cells and neurites at P1 in the cochlea

Genotype
MGI:5904347

cn25

• Allelic Composition: E2f4^tm2.1Lees/E2f4^tm2.1Lees; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S4/SvJae * 129S4/SvJaeSor * C57BL/6

respiratory system

abnormal respiratory motile cilium morphology ( J:241925 )

• mice are unable to form multiciliated cells and unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium

• however, primary cilia formation occurs

cellular

abnormal respiratory motile cilium morphology ( J:241925 )

• mice are unable to form multiciliated cells and unable to form deuterosomes and Pcm1-containing aggregates in lung epithelium

• however, primary cilia formation occurs

Genotype
MGI:5298087

cn26

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

integument

integument phenotype ( J:172048 )

N • no epidermal defects or tumor formation are observed with tamoxifen treatment at day 28 (during period of up to 4 months after cre induction) when hair follicles are in full anlagen

Genotype
MGI:5902322

cn27

• Allelic Composition: Yy1^tm2.1Yshi/Yy1^tm2.1Yshi; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:239777 )

• all newborns die at birth from respiratory failure

growth/size/body

lung cyst ( J:239777 )

• E18.5 lungs show the presence of dilated fluid-filled sacs

• proliferation assays in lungs from E18.5 fetuses show an increase in cell proliferation in cystic walls

• neither secretory club (Clara) cells or ciliated cells are seen in cyst epithelium at E18.5 and cysts are lined by Type II and Type I pneumocytes

• a microvascular network is present in the parenchyma forming the cyst walls

left pulmonary isomerism ( J:239777 )

• E12.5 lungs show two hypoplastic lobes instead of the expected asymmetric pattern of 4 right lobes and 1 left lobe

respiratory system

increased lung apoptosis ( J:239777 )

• apoptosis is increased in lung mesenchyme at E14.5

• E12.5 embryos cultured in vitro show increased apoptosis in the lung

• the addition of recombinant mouse SHH into the media rescues the increased apoptosis

abnormal lung morphology ( J:239777 )

• E18.5 lungs exhibit a disorganized architecture

lung cyst ( J:239777 )

• E18.5 lungs show the presence of dilated fluid-filled sacs

• proliferation assays in lungs from E18.5 fetuses show an increase in cell proliferation in cystic walls

• neither secretory club (Clara) cells or ciliated cells are seen in cyst epithelium at E18.5 and cysts are lined by Type II and Type I pneumocytes

• a microvascular network is present in the parenchyma forming the cyst walls

left pulmonary isomerism ( J:239777 )

• E12.5 lungs show two hypoplastic lobes instead of the expected asymmetric pattern of 4 right lobes and 1 left lobe

abnormal lung development ( J:239777 )

• marker analysis indicates altered patterning and cell differentiation in the lung

abnormal branching involved in lung morphogenesis ( J:239777 )

• branching morphogenesis in the lung is inhibited, however, distal epithelial cell differentiation is maintained

• E12.5 embryos cultured in vitro fail with branching of lung

• the addition of recombinant mouse SHH into the media does not rescue the branching defect

abnormal lung-associated mesenchyme development ( J:239777 )

• impairment of peribronchial smooth muscle differentiation as indicated by a lack of markers of airway smooth muscle differentiation around cysts

abnormal lung epithelium morphology ( J:239777 )

• lung epithelium exhibits an abnormal stratified structure at E12.5

decreased club cell number ( J:239777 )

• club (Clara) cells are scarce in the proximal airways

abnormal airway basal cell morphology ( J:239777 )

• basal cells are distributed irregularly along the proximal airways of embryos, although the number of basal cells is not altered

decreased respiratory mucosa goblet cell number ( J:239777 )

• goblet cells are scarce in the proximal airways

abnormal trachea morphology ( J:239777 )

• trachea is longer

• trachea is thinner with disorganized cartilage rings

abnormal tracheal ciliated epithelium morphology ( J:239777 )

• ciliated cells are scarce in the airways

abnormal tracheal cartilage morphology ( J:239777 )

• trachea shows abnormal formation of cartilage rings

trachea stenosis ( J:239777 )

respiratory failure ( J:239777 )

abnormal respiratory epithelium physiology ( J:239777 )

• reduction in lung epithelium proliferation at E12.5

cellular

increased lung apoptosis ( J:239777 )

• apoptosis is increased in lung mesenchyme at E14.5

• E12.5 embryos cultured in vitro show increased apoptosis in the lung

• the addition of recombinant mouse SHH into the media rescues the increased apoptosis

impaired myofibroblast differentiation ( J:239777 )

• differentiation of airway myofibroblasts is impaired

skeleton

abnormal tracheal cartilage morphology ( J:239777 )

• trachea shows abnormal formation of cartilage rings

Genotype
MGI:3718107

cn28

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Notch1)Dam}/Gt(ROSA)26Sor⁺; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac

vision/eye

vision/eye phenotype ( J:118372 )

N • retina size is normal

Genotype
MGI:3606229

cn29

• Allelic Composition: Fgfr1^tm3.2Cxd/Fgfr1^tm3.2Cxd; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac

limbs/digits/tail

oligodactyly ( J:101736 )

• at E18.5 a single digit (probably digit 3) is absent on autopods of both the fore and hindlimbs

abnormal embryonic autopod plate morphology ( J:101736 )

• at E11.5, limb bud size is normal but only 4 digit condensations are present and the 2 middle condensations are farther apart than normal

Genotype
MGI:3607119

cn30

• Allelic Composition: Fgfr1^tm3.1Cxd/Fgfr1^tm3.2Cxd; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac

limbs/digits/tail

oligodactyly ( J:101736 )

• at E18.5 a single digit (probably digit 3) is absent on autopods of both the fore and hindlimbs

abnormal embryonic autopod plate morphology ( J:101736 )

• at E11.5, limb bud size is normal but only 4 digit condensations are present and the 2 middle condensations are farther apart than normal

Genotype
MGI:5694209

cn31

• Allelic Composition: Gt(ROSA)26Sor^tm1(Fgf8)Lma/Gt(ROSA)26Sor⁺; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac

reproductive system

abnormal genital tubercle morphology ( J:223057 )

• larger than in controls

abnormal reproductive system physiology ( J:223057 )

• mice treated with tamoxifen at E10.5 exhibit increased mitotic index in mesoderm-derived para-cloacal mesenchyme compared with wild-type mice

Genotype
MGI:3810321

cn32

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Smo/EYFP)Amc}/Gt(ROSA)26Sor^{tm1(Smo/EYFP)Amc}; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

neoplasm

neoplasm ( J:139574 )

N • following induction with tamoxifen, mice do not exhibit medulloblastoma

Genotype
MGI:4461253

cn33

• Allelic Composition: Ar^tm2Ska/Y; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

reproductive system

reproductive system phenotype ( J:148515 )

♂N • tamoxifen-treated mice exhibit normal masculinization

Genotype
MGI:5495282

cn34

• Allelic Composition: Wnt1^tm1.1Mze/Wnt1^tm1.1Mze; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6N

nervous system

premature neuronal precursor differentiation ( J:194842 )

• significant increase of the number of differentiated MbDA neurons at E11.5

• significant increase in the number of Ki67+ progenitors in the differentiating zone in medial planes

abnormal midbrain morphology ( J:194842 )

• depletion of medial MbDA neurons and expansion of more laterally positioned MbDA neurons at E12.5

decreased neuron number ( J:194842 )

• depletion of medial MbDA neurons

cellular

premature neuronal precursor differentiation ( J:194842 )

• significant increase of the number of differentiated MbDA neurons at E11.5

• significant increase in the number of Ki67+ progenitors in the differentiating zone in medial planes

Genotype
MGI:4948658

cn35

• Allelic Composition: Pofut1^tm2Pst/Pofut1^tm1Pst; Shh^{tm2(cre/ERT2)Cjt}/Shh⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6J * SJL

mortality/aging

premature death ( J:150051 )

• only 1 of 17 pups survived until P28

postnatal lethality, incomplete penetrance ( J:150051 )

• pups failed to thrive and died within 2-3 weeks of life

growth/size/body

decreased birth body size ( J:150051 )

• at birth, pups appeared grossly normal but were already smaller than control littermates

decreased body size ( J:150051 )

• pups failed to thrive and by P21 were much smaller than control littermates

respiratory system

respiratory system phenotype ( J:150051 )

N • at E11.5, E14.5 and E18.5, mutant lungs showed normal gross morphology and size relative to control lungs

N • no defects in the branching pattern were detected when E11.5 lungs were cultured for 24 and 48 hrs

N • distal epithelium differentiation (formation of alveolar sacs and type I and type II cells) remained unaffected

N • normal formation of goblet cells was observed in the trachea at birth (P0)

N • the distribution and number of basal cells remained normal

lung inflammation ( J:150051 )

• by P21, isolated foci of inflammatory cells, including macrophages, were seen in the bronchiolar epithelium, unlike in control lungs

abnormal respiratory epithelium morphology ( J:150051 )

• at P7, P14 and P21, a severely attenuated airway epithelium is noted in medium-sized airways and in terminal bronchioles

• at E18.5, the respiratory epithelium was populated almost exclusively by beta-tubulin-expressing ciliated cells, unlike in control lungs where ciliated cells were interspersed with secretory Clara cells

• at E18.5, Foxj1-positive ciliated cells comprised 80-85% of the population of the airway epithelium, regardless of the airway generation, unlike in control lungs where Foxj1-expressing cells averaged 40%, 18% and 17% of epithelial cells seen in the large, medium and small airways, respectively

• at E18.5, Ki67 labeling averaged 15%, 10% and 5% of control values in large, medium and small airways, respectively, suggesting a substantial decrease in epithelial cell proliferation

abnormal bronchiole epithelium morphology ( J:150051 )

• by P21, a thin metaplastic squamous epithelium, scattered cell debris and isolated macrophages were observed instead of the typical cuboidal epithelium seen in control bronchioles

• however, none of these changes were apparent at birth or at E18.5

absent club cells ( J:150051 )

• no secretory Clara cells were detected at E18.5 and P0, as determined by specific marker expression analysis

• however, no differences in apoptosis were noted at E14.5, E18.5 and P0 lungs

immune system

lung inflammation ( J:150051 )

• by P21, isolated foci of inflammatory cells, including macrophages, were seen in the bronchiolar epithelium, unlike in control lungs

nervous system

increased solitary pulmonary neuroendocrine cell number ( J:150051 )

• at E18.5, the number of neuroendocrine cells is significantly increased in mutant airways, as shown by Pgp9.5 immunostaining

endocrine/exocrine glands

increased solitary pulmonary neuroendocrine cell number ( J:150051 )

• at E18.5, the number of neuroendocrine cells is significantly increased in mutant airways, as shown by Pgp9.5 immunostaining

Genotype
MGI:3513048

cn36

• Allelic Composition: Disp1^icb/Disp1^tm2Amc; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129/Sv * C57BL/6J * SWR

mortality/aging

neonatal lethality ( J:94270 )

craniofacial

absent parietal bone ( J:94270 )

absent premaxilla ( J:94270 )

abnormal nasal pit morphology ( J:94270 )

• fusion of the nasal pits

abnormal facial morphology ( J:94270 )

• facial midline defects are seen

skeleton

absent parietal bone ( J:94270 )

absent premaxilla ( J:94270 )

nervous system

abnormal neuron differentiation ( J:94270 )

• pMN and pV3 progenitor cells are found at the midline and are reduced in numbers to less than 10% wild-type

absent floor plate ( J:94270 )

embryo

absent floor plate ( J:94270 )

respiratory system

abnormal nasal pit morphology ( J:94270 )

• fusion of the nasal pits

cellular

abnormal neuron differentiation ( J:94270 )

• pMN and pV3 progenitor cells are found at the midline and are reduced in numbers to less than 10% wild-type

growth/size/body

abnormal facial morphology ( J:94270 )

• facial midline defects are seen

Genotype
MGI:3513044

cn37

• Allelic Composition: Disp1^tm2.1Amc/Disp1^tm2Amc; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129/Sv * C57BL/6J * SWR

mortality/aging

neonatal lethality ( J:94270 )

craniofacial

abnormal parietal bone morphology ( J:94270 )

• ossification of the parietal bone is delayed

absent premaxilla ( J:94270 )

abnormal nasal pit morphology ( J:94270 )

• abnormally close association of the nasal pits

abnormal facial morphology ( J:94270 )

• facial midline defects are seen

skeleton

abnormal parietal bone morphology ( J:94270 )

• ossification of the parietal bone is delayed

absent premaxilla ( J:94270 )

nervous system

abnormal neuron differentiation ( J:94270 )

• the ventral midline cells are an intermediate state between pV3 and floor plate and fewer ventral progenitor cells are seen

respiratory system

abnormal nasal pit morphology ( J:94270 )

• abnormally close association of the nasal pits

cellular

abnormal neuron differentiation ( J:94270 )

• the ventral midline cells are an intermediate state between pV3 and floor plate and fewer ventral progenitor cells are seen

growth/size/body

abnormal facial morphology ( J:94270 )

• facial midline defects are seen

Genotype
MGI:5544581

cn38

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129X1/SvJ

respiratory system

abnormal lung vasculature morphology ( J:204743 )

• in absence of lung formation, the pulmonary vascular plexus persists throughout embryonic development, but does not branch or develop further

tracheoesophageal fistula ( J:153098 )

abnormal lung development ( J:204743 )

• lungs fail to develop from the foregut

absent lungs ( J:204743 )

• lung agenesis is found in embryos examined at E13.5 and E17.5

cardiovascular system

cardiovascular system phenotype ( J:204743 )

N • although no lungs develop, heart development and outflow and inflow tract structures are relatively normal, including atrial septation, septation between aorta and the pulmonary trunk, and atrioventricular canal development

abnormal pulmonary artery morphology ( J:204743 )

• primitive non-branched pulmonary arteries which flank the esophagus and originate from the pulmonary trunk persist in E17.5 embryos

• pulmonary veins and pulmonary arteries develop and intersect at approximate location where a lung bud would be present in a normal embryo

abnormal lung vasculature morphology ( J:204743 )

• in absence of lung formation, the pulmonary vascular plexus persists throughout embryonic development, but does not branch or develop further

abnormal pulmonary vein morphology ( J:204743 )

digestive/alimentary system

tracheoesophageal fistula ( J:153098 )

Genotype
MGI:3054017

cn39

• Allelic Composition: Disp1^icb/Disp1^tm1Amc; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

limbs/digits/tail

oligodactyly ( J:92504 )

• digit 2 is absent, all other digits are present

Genotype
MGI:3777639

cn40

• Allelic Composition: Gt(ROSA)26Sor^{tm4(CAG-lacZ,-EGFP)Dym}/Gt(ROSA)26Sor⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: involves: C57BL/6

integument

abnormal skin morphology ( J:132568 )

• the mean overall thickness of the skin of E18.5 embryos is reduced by 10% compared to wild-type embryos

thin epidermis ( J:132568 )

• the mean thickness of the epidermis of E18.5 embryos is slightly but significantly reduced by 4% compared to wild-type embyros

Genotype
MGI:5694220

cn41

• Allelic Composition: Gt(ROSA)26Sor^tm2(Sp8)Lma/Gt(ROSA)26Sor⁺; Shh^{tm1(EGFP/cre)Cjt}/Shh⁺
• Genetic Background: Not Specified

limbs/digits/tail

limbs/digits/tail phenotype ( J:223057 )

N • mice exhibit normal appendage development

Genotype
MGI:3583774

cx42

• Allelic Composition: Ccd/Ccd⁺; Shh^Dsh/Shh⁺
• Genetic Background: involves: 101 * C3H * C57BL * C57BL/10Rl * SEC

mortality/aging

premature death ( J:16170 )

• about 50% die before 8 weeks of age

skeleton

abnormal cranium morphology ( J:16170 )

abnormal neurocranium morphology ( J:16170 )

• very large, almost round, hole between the frontals and parietals and large hole between the parietals and interparietals

• the number of extra bones subdivided off between middle of parietals and interparietal bone is higher than in the single heterozygous Shh^Dsh mutant

abnormal interparietal bone morphology ( J:16170 )

• 9 of 11 show interparietal bone that is divided into 2 or more pieces and the width and length of the bone is decreased by 41% and 31%, respectively

occipital bone foramen ( J:16170 )

• occipital foramen with peculiar wide indentation on the dorsal side

abnormal temporal bone squamous part morphology ( J:16170 )

• absent or greatly reduced ventral branch of the posttympanic hook of the squamosal

abnormal orbit morphology ( J:16170 )

• large gap between the jugal and squamosal bones making the orbit around the eye incomplete

abnormal maxilla morphology ( J:16170 )

• large (in 1 of 11), medium (in 5 of 11) and small (in 5 of 11) stalactite bones are seen on the maxilla

absent nasal bone ( J:16170 )

• jagged edge at anterior end of nasals caused by absence of bone

abnormal humerus morphology ( J:16170 )

absent deltoid tuberosity ( J:16170 )

• mostly on the right side (in 7 of 11) though seen also bilaterally (in 2 of 11)

abnormal pectoral girdle bone morphology ( J:16170 )

abnormal clavicle morphology ( J:16170 )

• incomplete clavicles

abnormal scapula morphology ( J:16170 )

• 9 of 11 show greatly indented anterior border of the scapula on the left side

abnormal xiphoid process morphology ( J:16170 )

• xiphisternum is 50-75% of the normal length, wider than normal, and is curved ventrally

abnormal pelvic girdle bone morphology ( J:16170 )

abnormal ischium morphology ( J:16170 )

• 5 of 11 have one or more ischia that are crooked (bent laterally) and 10 of 11 have an ischium and pubis that do not connect on at least one side of the body

abnormal pubis morphology ( J:16170 )

• 10 of 11 have an ischium and pubis that do not connect on at least one side of the body

abnormal vertebrae morphology ( J:16170 )

• dorsal dyssymphysis of the 9 most anterior vertebrae

abnormal ventral tubercle of atlas morphology ( J:16170 )

• most of the ventral tubercles of the atlas are unattached or weakly attached to the rest of the vertebra

fusion of atlas and odontoid process ( J:16170 )

• the odontoid peg is not connected to the axis but fuses to the ventral inside of the atlas

limbs/digits/tail

brachydactyly ( J:16170 )

• all 2nd through 5th digits are short

syndactyly ( J:16170 )

• 5 of 11 have metatarsal-phalanx 1 fusion on digit 4

abnormal humerus morphology ( J:16170 )

absent deltoid tuberosity ( J:16170 )

• mostly on the right side (in 7 of 11) though seen also bilaterally (in 2 of 11)

abnormal hindlimb morphology ( J:16170 )

• bony deposits in tissue behind calcaneus

craniofacial

abnormal cranium morphology ( J:16170 )

abnormal neurocranium morphology ( J:16170 )

• very large, almost round, hole between the frontals and parietals and large hole between the parietals and interparietals

• the number of extra bones subdivided off between middle of parietals and interparietal bone is higher than in the single heterozygous Shh^Dsh mutant

abnormal interparietal bone morphology ( J:16170 )

• 9 of 11 show interparietal bone that is divided into 2 or more pieces and the width and length of the bone is decreased by 41% and 31%, respectively

occipital bone foramen ( J:16170 )

• occipital foramen with peculiar wide indentation on the dorsal side

abnormal temporal bone squamous part morphology ( J:16170 )

• absent or greatly reduced ventral branch of the posttympanic hook of the squamosal

abnormal orbit morphology ( J:16170 )

• large gap between the jugal and squamosal bones making the orbit around the eye incomplete

abnormal maxilla morphology ( J:16170 )

• large (in 1 of 11), medium (in 5 of 11) and small (in 5 of 11) stalactite bones are seen on the maxilla

absent nasal bone ( J:16170 )

• jagged edge at anterior end of nasals caused by absence of bone

vision/eye

abnormal orbit morphology ( J:16170 )

• large gap between the jugal and squamosal bones making the orbit around the eye incomplete

growth/size/body

absent nasal bone ( J:16170 )

• jagged edge at anterior end of nasals caused by absence of bone

respiratory system

absent nasal bone ( J:16170 )

• jagged edge at anterior end of nasals caused by absence of bone

Genotype
MGI:5613161

cx43

• Allelic Composition: Rr29^tm1.1Bobh/Rr29⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

limbs/digits/tail

abnormal limb morphology ( J:208849 )

• range of limb phenotypes similar to mice homozygous for Rr29^tm1.1Bobh

oligodactyly ( J:208849 )

• 40% of mice have 4 digits, 30% have 4 phalanges and 3 metatarsels, 10% have 3 digits and 20% have 3 sets of phalanges and 2 metatarsels

Genotype
MGI:3812210

cx44

• Allelic Composition: Shh^tm1Chg/Shh⁺; Sulf1^Gt(XM190)Byg/Sulf1^Gt(XM190)Byg; Sulf2^{Gt(PST111)Byg}/Sulf2^{Gt(PST111)Byg}
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * C57BL/10

craniofacial

abnormal craniofacial morphology ( J:130163 )

• agnathic mice exhibit a narrow craniofacial region

absent mandible ( J:130163 )

• in 3 of 126 mice age E14.5 to E18.5

short mandible ( J:130163 )

• in 2 of 126 mice age E14.5 to E18.5

vision/eye

microphthalmia ( J:130163 )

• agnathic mice exhibit small or absent eyes

anophthalmia ( J:130163 )

• agnathic mice exhibit small or absent eyes

skeleton

absent mandible ( J:130163 )

• in 3 of 126 mice age E14.5 to E18.5

short mandible ( J:130163 )

• in 2 of 126 mice age E14.5 to E18.5

Genotype
MGI:5292679

cx45

• Allelic Composition: Nr5a1^tm1.1Hain/Nr5a1^tm1.1Hain; Shh^tm1Amc/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

homeostasis/metabolism

abnormal aldosterone level ( J:175843 )

• decreased adrenal aldosterone levels

• decrease is less severe than in mice homozygous for Nr5a1^tm1.1Hain alone

Genotype
MGI:5447986

cx46

• Allelic Composition: Hhat^{Tg(TFAP2A-cre)1Will}/Hhat⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

craniofacial

abnormal craniofacial morphology ( J:190013 )

• E17.5-18.5 embryos have craniofacial defects that are not consistent with holoprosencephaly showing that the transgene did not insert into Shh.

Genotype
MGI:5562302

cx47

• Allelic Composition: Rr26^tm1Svok/Rr26^tm1Svok; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

limbs/digits/tail

limbs/digits/tail phenotype ( J:207959 )

N • mice exhibit normal hands and feet

Genotype
MGI:5827502

cx48

• Allelic Composition: Shh⁺/Shh^tm1Chg; Zic2^Ku/Zic2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cAnNCrl * C3H/HeH

normal phenotype

no abnormal phenotype detected ( J:138862 )

• trans-heterozygotes do not exhibit any defects characteristic of either single homozygote

Genotype
MGI:5751502

cx49

• Allelic Composition: Shh^tm1Chg/Shh⁺; Vps25^m1Lis/Vps25^m1Lis
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J

craniofacial

mandible hypoplasia ( J:223082 )

• as in Vps25^m1Lis homozygotes

short snout ( J:223082 )

• stunted as in Vps25^m1Lis homozygotes

abnormal outer ear morphology ( J:223082 )

• as in Vps25^m1Lis homozygotes

growth/size/body

short snout ( J:223082 )

• stunted as in Vps25^m1Lis homozygotes

abnormal outer ear morphology ( J:223082 )

• as in Vps25^m1Lis homozygotes

limbs/digits/tail

polydactyly ( J:223082 )

• partial rescue of polydactyly observed in Vps25^m1Lis homozygotes

skeleton

mandible hypoplasia ( J:223082 )

• as in Vps25^m1Lis homozygotes

hearing/vestibular/ear

abnormal outer ear morphology ( J:223082 )

• as in Vps25^m1Lis homozygotes

Genotype
MGI:3589447

cx50

• Allelic Composition: Ndst1^tm1.1Grob/Ndst1⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

mandible hypoplasia ( J:100425 )

• at E15.5, 4 of 8 mutants display hyploplastic lower jaws

frontonasal prominence hypoplasia ( J:100425 )

• at E15.5, 4 of 8 mutants display hypoplastic frontonasal or maxillary processes

abnormal maxillary prominence morphology ( J:100425 )

• at E15.5, 4 of 8 mutants display hypoplastic frontonasal or maxillary processes

absent tongue ( J:100425 )

• at E15.5, 4 of 8 mutants lack a tongue

absent olfactory epithelium ( J:100425 )

• at E15.5, 4 of 8 mutants lack olfactory epithelium

small snout ( J:100425 )

• surviving mutants generally have a smaller snout

vision/eye

aphakia ( J:100425 )

• at E15.5, 4 of 8 mutants display absent or hypoplastic eye lenses

abnormal eye development ( J:100425 )

• at E15.5, 4 of 8 mutants display severe eye developmental defects

microphthalmia ( J:100425 )

• surviving mutants generally have smaller eyes

digestive/alimentary system

absent tongue ( J:100425 )

• at E15.5, 4 of 8 mutants lack a tongue

taste/olfaction

absent olfactory epithelium ( J:100425 )

• at E15.5, 4 of 8 mutants lack olfactory epithelium

skeleton

mandible hypoplasia ( J:100425 )

• at E15.5, 4 of 8 mutants display hyploplastic lower jaws

respiratory system

absent olfactory epithelium ( J:100425 )

• at E15.5, 4 of 8 mutants lack olfactory epithelium

growth/size/body

absent tongue ( J:100425 )

• at E15.5, 4 of 8 mutants lack a tongue

absent olfactory epithelium ( J:100425 )

• at E15.5, 4 of 8 mutants lack olfactory epithelium

small snout ( J:100425 )

• surviving mutants generally have a smaller snout

Genotype
MGI:3589448

cx51

• Allelic Composition: Ndst1^tm1.1Grob/Ndst1^tm1.1Grob; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

prenatal lethality ( J:100425 )

• 3-times fewer than expected mutants are produced

craniofacial

frontonasal prominence hypoplasia ( J:100425 )

• 4 of 5 mutants display severely hypoplastic frontonasal prominences similar to defects seen in severely affected Ndst1^tm1.1Grob single homozygotes

abnormal maxillary prominence morphology ( J:100425 )

• 4 of 5 mutants display severely hypoplastic maxillary prominences similar to defects seen in severely affected Ndst1^tm1.1Grob single homozygotes

nervous system

abnormal midbrain morphology ( J:100425 )

• all mutants display collapse of the midbrain

abnormal forebrain morphology ( J:100425 )

• all mutants display collapse of the forebrain

Genotype
MGI:3814907

cx52

• Allelic Composition: Six3^tm3.1Gco/Six3⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

holoprosencephaly ( J:140315 )

• 75% display a phenotype typical of holoprosencephaly after one backcross to C57BL/6

• after five backcrosses to C57BL/6, 100% show a holoprosencephaly phenotype

abnormal telencephalon morphology ( J:140315 )

• a single ganglionic eminence

• telencephalon is smaller at E10.5 than in controls

• reduced apoptosis in the ventral midline at E10.5

• increased apoptosis in the lateral dorsal telencephalon

abnormal cerebral hemisphere morphology ( J:140315 )

• cerebral hemispheres fused rostrally

absent corpus callosum ( J:140315 )

• at E17.5

olfactory bulb hypoplasia ( J:140315 )

• hypoplasia

craniofacial

abnormal medial nasal prominence morphology ( J:140315 )

• defective separation of the medial nasal prominence at E11.5

abnormal palatal shelf fusion at midline ( J:140315 )

• fusion defects in the secondary palate

absent philtrum ( J:140315 )

• absence of philtrum at E17.5

absent nasal septum ( J:140315 )

• no cartilaginous nasal septum at E17.5

respiratory system

absent nasal septum ( J:140315 )

• no cartilaginous nasal septum at E17.5

vision/eye

abnormal optic stalk morphology ( J:140315 )

• reduced apoptosis at E10.5

ocular hypotelorism ( J:140315 )

• shorter distance between the eyes at E11.5

digestive/alimentary system

abnormal palatal shelf fusion at midline ( J:140315 )

• fusion defects in the secondary palate

growth/size/body

abnormal palatal shelf fusion at midline ( J:140315 )

• fusion defects in the secondary palate

absent philtrum ( J:140315 )

• absence of philtrum at E17.5

absent nasal septum ( J:140315 )

• no cartilaginous nasal septum at E17.5

microcephaly ( J:140315 )

• at E11.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 2		DOID:0110872	OMIM:157170	J:140315

Genotype
MGI:7386875

cx53

• Allelic Composition: Gas1^tm1Fan/Gas1^tm1Fan; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:122159 )

craniofacial

abnormal craniofacial bone morphology ( J:122159 )

• perinatal skulls show exacerbated neurocranial, splanchnocranial, and dermatocranial defects relative to the single Gas1^tm1Fan homozygotes

• midline craniofacial phenotype is significantly worsened relative to that in single Gas1^tm1Fan homozygotes

abnormal Meckel's cartilage morphology ( J:122159 )

• Meckels cartilage is truncated and lacks a malleal end; the proximal end is slightly bifurcated

short Meckel's cartilage ( J:122159 )

small cranium ( J:122159 )

• perinatal skull size is reduced

abnormal neurocranium morphology ( J:122159 )

• neurocranial base development is severely disrupted: the trabecular basal plate, which runs from the rostral basisphenoid, presphenoid, and ethmoid through the nasal septum, is discontinuous and cleft

• all lateral extensions from the neurocranial base are disrupted: the ala temporali are hypoplastic, the lamina obturans fail to invest the cartilage of the ala, and ectopic preotic cartilaginous pillars extend toward the crista parotica of the otic capsule

abnormal basisphenoid bone morphology ( J:122159 )

• at E18.5, 75% of mice exhibit clefting of the basisphenoid

alisphenoid bone hypoplasia ( J:122159 )

• the ala temporali are hypoplastic

abnormal temporal bone morphology ( J:122159 )

• squamosal bones are repatterned and separated into distinct retrotympanic and squamosal portions

abnormal incisor morphology ( J:122159 )

• at E18.5, 25% of mice show fusion of the premaxillary incisors, 75% of mice show premaxillary incisor agenesis, and 75% show fusion of the mandibular incisors

abnormal lower incisor morphology ( J:122159 )

• at E18.5, the distal dentary contains a single lower incisor

abnormal molar morphology ( J:122159 )

• at E18.5, the duplicated proximal dentary includes an alveolus containing an ectopic molar

abnormal mandible morphology ( J:122159 )

• at E18.5, the proximal dentary appears to be duplicated and includes a secondary cartilage-containing condylar process and an alveolus containing an ectopic molar

• the distal dentary is synostotic across the midline and contains a single lower incisor

absent mandibular symphysis ( J:122159 )

• at E18.5, the distal dentary lacks a symphysis as it is synostotic across the midline; 75% of mice exhibit a synostotic mandible/symphysis phenotype

abnormal premaxilla morphology ( J:122159 )

• at E18.5, premaxillaries are hypoplastic, synostotic, and lack incisor teeth

premaxilla hypoplasia ( J:122159 )

absent incus ( J:122159 )

absent gonial bone ( J:122159 )

• gonial bones fail to form

absent malleus ( J:122159 )

abnormal stapes morphology ( J:122159 )

• a vestigial stapes is observed

abnormal nasal capsule morphology ( J:122159 )

• nasal capsules and associated dermal ossifications are severely reduced, without proper midline manifestations

cleft secondary palate ( J:122159 )

• at E18.5, all (100%) of mice exhibit complete secondary cleft palate

single external naris ( J:122159 )

• mice survive to birth but only have a single external nostril

growth/size/body

abnormal incisor morphology ( J:122159 )

• at E18.5, 25% of mice show fusion of the premaxillary incisors, 75% of mice show premaxillary incisor agenesis, and 75% show fusion of the mandibular incisors

abnormal lower incisor morphology ( J:122159 )

• at E18.5, the distal dentary contains a single lower incisor

abnormal molar morphology ( J:122159 )

• at E18.5, the duplicated proximal dentary includes an alveolus containing an ectopic molar

abnormal nasal capsule morphology ( J:122159 )

• nasal capsules and associated dermal ossifications are severely reduced, without proper midline manifestations

cleft secondary palate ( J:122159 )

• at E18.5, all (100%) of mice exhibit complete secondary cleft palate

single external naris ( J:122159 )

• mice survive to birth but only have a single external nostril

nervous system

holoprosencephaly ( J:122159 )

• mice exhibit a more severe holoprosencephaly phenotype than single Gas1^tm1Fan homozygotes

respiratory system

abnormal nasal capsule morphology ( J:122159 )

• nasal capsules and associated dermal ossifications are severely reduced, without proper midline manifestations

single external naris ( J:122159 )

• mice survive to birth but only have a single external nostril

skeleton

abnormal craniofacial bone morphology ( J:122159 )

• perinatal skulls show exacerbated neurocranial, splanchnocranial, and dermatocranial defects relative to the single Gas1^tm1Fan homozygotes

• midline craniofacial phenotype is significantly worsened relative to that in single Gas1^tm1Fan homozygotes

abnormal Meckel's cartilage morphology ( J:122159 )

• Meckels cartilage is truncated and lacks a malleal end; the proximal end is slightly bifurcated

short Meckel's cartilage ( J:122159 )

small cranium ( J:122159 )

• perinatal skull size is reduced

abnormal neurocranium morphology ( J:122159 )

• neurocranial base development is severely disrupted: the trabecular basal plate, which runs from the rostral basisphenoid, presphenoid, and ethmoid through the nasal septum, is discontinuous and cleft

• all lateral extensions from the neurocranial base are disrupted: the ala temporali are hypoplastic, the lamina obturans fail to invest the cartilage of the ala, and ectopic preotic cartilaginous pillars extend toward the crista parotica of the otic capsule

abnormal basisphenoid bone morphology ( J:122159 )

• at E18.5, 75% of mice exhibit clefting of the basisphenoid

alisphenoid bone hypoplasia ( J:122159 )

• the ala temporali are hypoplastic

abnormal temporal bone morphology ( J:122159 )

• squamosal bones are repatterned and separated into distinct retrotympanic and squamosal portions

abnormal incisor morphology ( J:122159 )

• at E18.5, 25% of mice show fusion of the premaxillary incisors, 75% of mice show premaxillary incisor agenesis, and 75% show fusion of the mandibular incisors

abnormal lower incisor morphology ( J:122159 )

• at E18.5, the distal dentary contains a single lower incisor

abnormal molar morphology ( J:122159 )

• at E18.5, the duplicated proximal dentary includes an alveolus containing an ectopic molar

abnormal mandible morphology ( J:122159 )

• at E18.5, the proximal dentary appears to be duplicated and includes a secondary cartilage-containing condylar process and an alveolus containing an ectopic molar

• the distal dentary is synostotic across the midline and contains a single lower incisor

absent mandibular symphysis ( J:122159 )

• at E18.5, the distal dentary lacks a symphysis as it is synostotic across the midline; 75% of mice exhibit a synostotic mandible/symphysis phenotype

abnormal premaxilla morphology ( J:122159 )

• at E18.5, premaxillaries are hypoplastic, synostotic, and lack incisor teeth

premaxilla hypoplasia ( J:122159 )

absent incus ( J:122159 )

absent gonial bone ( J:122159 )

• gonial bones fail to form

absent malleus ( J:122159 )

abnormal stapes morphology ( J:122159 )

• a vestigial stapes is observed

abnormal nasal capsule morphology ( J:122159 )

• nasal capsules and associated dermal ossifications are severely reduced, without proper midline manifestations

synostosis ( J:122159 )

• at E18.5, 100% of premaxillaries are synostotic

premature coronal suture closure ( J:122159 )

• no patent sutures between the frontal and parietal ossifications are observed

hearing/vestibular/ear

abnormal middle ear morphology ( J:122159 )

• middle ear-associated splanchnocranial elements either fail to develop (malleus and incus) or are represented by a cartilaginous remnant (stapes)

• dermatocranial elements (ectotympanic and gonial bones) fail to form

absent incus ( J:122159 )

absent gonial bone ( J:122159 )

• gonial bones fail to form

absent malleus ( J:122159 )

abnormal stapes morphology ( J:122159 )

• a vestigial stapes is observed

absent tympanic ring ( J:122159 )

• ectotympanic bones fail to form

digestive/alimentary system

cleft secondary palate ( J:122159 )

• at E18.5, all (100%) of mice exhibit complete secondary cleft palate

Genotype
MGI:6144003

cx54

• Allelic Composition: Rr45^tm1.1Tshir/Rr45⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/JNCrlj

skeleton

epiglottis hypoplasia ( J:148018 )

abnormal arytenoid cartilage morphology ( J:148018 )

respiratory system

epiglottis hypoplasia ( J:148018 )

abnormal arytenoid cartilage morphology ( J:148018 )

digestive/alimentary system

epiglottis hypoplasia ( J:148018 )

Genotype
MGI:4948512

cx55

• Allelic Composition: Rr117^tm1.1Dje/Rr117⁺; Shh^tm1Amc/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * FVB/N

mortality/aging

postnatal lethality, incomplete penetrance ( J:170540 )

• 80% of mice fail to gain weight and die by 7 days of age

• 20% survive to adulthood

growth/size/body

slow postnatal weight gain ( J:170540 )

• 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

behavior/neurological phenotype ( J:170540 )

N • normal suckling response

N • dead pups often have milk in their stomach

N • well coordinated motor control

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170540 )

N • normal blood glucose

Genotype
MGI:3711885

cx56

• Allelic Composition: Gas1^tm2Fan/Gas1⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system

increased neuronal precursor cell number ( J:121553 )

• pMN motorneuron progenitor cell numbers are increased

Genotype
MGI:3711884

cx57

• Allelic Composition: Gas1^tm2Fan/Gas1^tm2Fan; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

limbs/digits/tail

forelimb oligodactyly ( J:121553 )

• digit 2 or 3 is absent from the forelimbs

• however, long bones are normal

craniofacial

abnormal craniofacial morphology ( J:121553 )

• cranio-skeletal defects are more significant than those seen in Gas1^tm2Fan homozygotes

short mandible ( J:121553 )

• profound truncation

abnormal nose morphology ( J:121553 )

• at E18.5, complete fusion of medial nasal processes

nervous system

abnormal floor plate morphology ( J:121553 )

• floor plate cells adopt more dorsal fates, as shown by marker staining, than Gas1^tm2Fan homozygotes

abnormal innervation ( J:121553 )

• axonal projections are misrouted through the Isl1/2+ motor column

decreased neuronal precursor cell number ( J:121553 )

• vp3 interneuron progenitors are reduced further compared to Gas1^tm2Fan homozygotes

• pMN motorneuron progenitors are dramatically reduced although their relative dorsal position to vp3 interneuron progenitors is preserved

• however, pMN specification occurs normally

skeleton

short mandible ( J:121553 )

• profound truncation

abnormal intervertebral disk morphology ( J:121553 )

• partial fusion of intervertebral discs

abnormal vertebral body morphology ( J:121553 )

• reduction in the ossification centers

respiratory system

abnormal nose morphology ( J:121553 )

• at E18.5, complete fusion of medial nasal processes

growth/size/body

abnormal nose morphology ( J:121553 )

• at E18.5, complete fusion of medial nasal processes

decreased fetal size ( J:121553 )

embryo

abnormal floor plate morphology ( J:121553 )

• floor plate cells adopt more dorsal fates, as shown by marker staining, than Gas1^tm2Fan homozygotes

Genotype
MGI:7367584

cx58

• Allelic Composition: Rr115^em1Bobh/Rr115⁺; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

craniofacial

basisphenoid bone hypoplasia ( J:306254 )

• reduced in size or absent in E17.5 embryos

abnormal pterygoid bone morphology ( J:306254 )

• in E17.5 embryos

abnormal maxilla morphology ( J:306254 )

• in E17.5 embryos

vomer bone hypoplasia ( J:306254 )

• excessively fused or absent in E17.5 embryos

abnormal nasal cavity morphology ( J:306254 )

• reduced length in E17.5 embryos

round head ( J:306254 )

• in E17.5 embryos

endocrine/exocrine glands

abnormal magnocellular neurosecretory cell morphology ( J:306254 )

• absent oxytocin and vasopressin expressing cells in paraventricular nucleus (PVN) in E15.5 embryos

abnormal parvocellular neurosecretory cell morphology ( J:306254 )

• absent oxytocin, tyrosine hydroxylase (TH1) and vasopressin expressing cells in paraventricular nucleus (PVN) in E15.5 embryos

abnormal adenohypophysis development ( J:306254 )

• mislocated in E17.5 embryos, intercepting the basisphenoid bone

abnormal Rathke's pouch development ( J:306254 )

• shifted ventrally in E11.5 embryos

• severely malformed in E13.5 embryos

abnormal neurohypophysis development ( J:306254 )

• less separation of infundibulum from neuroectodermal tissue in E13.5 embryos

• undergoing apoptosis in E17.5 embryos

ectopic neurohypophysis ( J:306254 )

• infundibulum shifted ventrally in E11.5 embryos, remaining ectopic in E15.5 embryos

growth/size/body

abnormal nasal cavity morphology ( J:306254 )

• reduced length in E17.5 embryos

round head ( J:306254 )

• in E17.5 embryos

mortality/aging

perinatal lethality, complete penetrance ( J:306254 )

• expected Mendelian ratios at stage E17.5

• premature death by age P4

nervous system

abnormal adenohypophysis development ( J:306254 )

• mislocated in E17.5 embryos, intercepting the basisphenoid bone

abnormal Rathke's pouch development ( J:306254 )

• shifted ventrally in E11.5 embryos

• severely malformed in E13.5 embryos

abnormal neurohypophysis development ( J:306254 )

• less separation of infundibulum from neuroectodermal tissue in E13.5 embryos

• undergoing apoptosis in E17.5 embryos

ectopic neurohypophysis ( J:306254 )

• infundibulum shifted ventrally in E11.5 embryos, remaining ectopic in E15.5 embryos

abnormal hypothalamus morphology ( J:306254 )

• midline hypothalamic brain tissue absent in E17.5 embryos

abnormal magnocellular neurosecretory cell morphology ( J:306254 )

• absent oxytocin and vasopressin expressing cells in paraventricular nucleus (PVN) in E15.5 embryos

abnormal parvocellular neurosecretory cell morphology ( J:306254 )

• absent oxytocin, tyrosine hydroxylase (TH1) and vasopressin expressing cells in paraventricular nucleus (PVN) in E15.5 embryos

respiratory system

abnormal nasal cavity morphology ( J:306254 )

• reduced length in E17.5 embryos

skeleton

basisphenoid bone hypoplasia ( J:306254 )

• reduced in size or absent in E17.5 embryos

abnormal pterygoid bone morphology ( J:306254 )

• in E17.5 embryos

abnormal maxilla morphology ( J:306254 )

• in E17.5 embryos

vomer bone hypoplasia ( J:306254 )

• excessively fused or absent in E17.5 embryos

Genotype
MGI:3665550

cx59

• Allelic Composition: Shh^tm1Chg/Shh⁺; Tg(Shh)#Dje/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellum morphology ( J:94461 )

• partial loss of Shh partially rescues Tg(Shh)#Dje phenotype; at E18.5, in some animals, cerebellum is slightly smaller than that of transgenics alone

abnormal cerebellar granule layer morphology ( J:94461 )

• IGL is not as thick or irregular as that of Shh transgenic mice and overall size is reduced

Genotype
MGI:6113949

cx60

• Allelic Composition: Shh^{tm1(EGFP/cre)Cjt}/Shh⁺; Sox17^tm1Ysk/Sox17⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6

endocrine/exocrine glands

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant

muscle

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant

liver/biliary system

abnormal gallbladder smooth muscle morphology ( J:241569 )

• formation of smooth muscle layers in gallbladders is more severely delayed and defective than in either single mutant

Genotype
MGI:3711877

cx61

• Allelic Composition: Gas1^tm2Fan/Gas1^tm2Fan; Shh^tm1Chg/Shh⁺
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J

limbs/digits/tail

oligodactyly ( J:121554 )

• 16% of forelimbs have 4.5 digits, 84% of forelimbs and 100% of hindlimbs are missing digit 2

• no digit forms at the digit 2 position

nervous system

holoprosencephaly ( J:121554 )

• mild, with a narrowing and fusion of the midline facial structures

respiratory system

single external naris ( J:121554 )

• single nostril

craniofacial

single external naris ( J:121554 )

• single nostril

growth/size/body

single external naris ( J:121554 )

• single nostril

Genotype
MGI:3513050

cx62

• Allelic Composition: Disp1^tm2.1Amc/Disp1^tm2.1Amc; Shh^tm1Amc/Shh⁺
• Genetic Background: involves: 129/Sv * C57BL/6J * SWR

nervous system

abnormal neuron differentiation ( J:94270 )

• the reduction of pMN and pV2 progenitors results in a decrease in motorneuron precursors that are also abnormally positioned at the ventral midline

absent floor plate ( J:94270 )

• the floor plate is absent and the ventral midline has reduced numbers of the ventral most neural progenitors

embryo

absent floor plate ( J:94270 )

• the floor plate is absent and the ventral midline has reduced numbers of the ventral most neural progenitors

cellular

abnormal neuron differentiation ( J:94270 )

• the reduction of pMN and pV2 progenitors results in a decrease in motorneuron precursors that are also abnormally positioned at the ventral midline

Genotype
MGI:3052728

cx63

• Allelic Composition: Disp1^icb/Disp1^tm1Amc; Shh^tm1Amc/Shh⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

cardiovascular system

failure of heart looping ( J:92058 )

• no heart looping but normal embryo turning

nervous system

holoprosencephaly ( J:92058 )

abnormal neuron specification ( J:92058 )

• ventral midline of neural tube occupied by a reduced population of motor neuron progenitors

craniofacial

proboscis ( J:92058 )

• extreme proboscis-like nasal process

growth/size/body

proboscis ( J:92058 )

• extreme proboscis-like nasal process

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
holoprosencephaly 3		DOID:0110875	OMIM:142945	J:92058