Phenotypes associated with this allele

• Allele Symbol: Ptch1^tm1Mps
• Allele Name: targeted mutation 1, Matthew P Scott
• Allele ID: MGI:1857447
• Summary: 39 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ	MGI:4461985
hm2	Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:2655205
hm3	Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:2676434
ht4	Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:2675737
ht5	Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2173417
ht6	Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:2177702
ht7	Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J	MGI:6259595
ht8	Ptch1^dl/Ptch1^tm1Mps	involves: 129S1/SvImJ * 129X1/SvJ * C57BL/6J	MGI:5544603
cn9	Brca2^tm1Brn/Brca2^tm1Brn Ptch1^tm1Mps/Ptch1^+ Trp53^tm1Tyj/Trp53^tm1Tyj Tg(Nes-cre)1Kln/0	involves: 129 * C57BL/6 * SJL	MGI:3831343
cn10	Brca2^tm1Brn/Brca2^tm1Brn Ptch1^tm1Mps/Ptch1^+ Trp53^tm1Tyj/Trp53^+ Tg(Nes-cre)1Kln/0	involves: 129 * C57BL/6 * SJL	MGI:3831342
cn11	Ptch1^tm1Mps/Ptch1^+ Tg(Atoh1-sb11)1Mtay/0 TgTn(sb-T2/Onc3)12740Njen/0	involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J * ICR	MGI:5317025
cx12	Ptch1^tm1Mps/Ptch1^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129 * 129S2/SvPas * C57BL/6	MGI:3759458
cx13	Chmp1a^Gt(XC472)Byg/Chmp1a^Gt(XC472)Byg Ptch1^tm1Mps/Ptch1^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6514750
cx14	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3710324
cx15	Ptch1^tm1Mps/Ptch1^+ Ptch2^tm1Pmc/Ptch2^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6	MGI:3690370
cx16	Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6	MGI:5544755
cx17	Cdkn1b^tm1Mlf/Cdkn1b^+ Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6	MGI:5544754
cx18	Gli2^tm3.1Blnw/Gli2^tm3.1Blnw Ptch1^tm1Mps/?	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H * C57BL/6	MGI:5432799
cx19	Ptch1^tm1Mps/Ptch1^+ Tg(Shh)#Dje/0	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster	MGI:3665561
cx20	Hhip^tm1Amc/Hhip^tm1Amc Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:2675747
cx21	Hhat^Tg(TFAP2A-cre)1Will/Hhat^+ Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5447987
cx22	Disp1^tm1Amc/Disp1^tm1Amc Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3052724
cx23	Ptch1^tm1Mps/Ptch1^+ Shh^tm6Amc/Shh^tm6Amc	involves: 129S1/Sv * 129X1/SvJ	MGI:3783757
cx24	Mtss1^tm1Pla/Mtss1^tm1Pla Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ	MGI:5319221
cx25	Gli1^tm1Alj/Gli1^tm1Alj Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * Swiss Webster	MGI:3795858
cx26	Disp1^icb/Disp1^icb Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J	MGI:5803873
cx27	Ptch1^tm1Mps/Ptch1^tm1Mps Tmem107^schlei/Tmem107^schlei	involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J	MGI:5433092
cx28	Ptch1^tm1Mps/Ptch1^+ Ptch2^tm1Pmc/Ptch2^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3690366
cx29	Ihh^tm1Amc/Ihh^tm1Amc Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:7432575
cx30	Ptch1^tm1Mps/Ptch1^+ Ptch2^tm1Pmc/Ptch2^tm1Pmc	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3690367
cx31	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5544756
cx32	Ptch1^tm1Mps/Ptch1^+ Tg(Atoh1-GFP)1Jejo/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3836962
cx33	Ptch1^tm1Mps/Ptch1^tm1Mps Wdpcp^cys40/Wdpcp^cys40	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5558105
cx34	Dync2h1^lln/Dync2h1^lln Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3624275
cx35	Kif7^maki/Kif7^maki Ptch1^tm1Mps/Ptch1^tm1Mps Tg(Hlxb9-GFP)1Tmj/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:4355990
cx36	Hhip^tm1Amc/Hhip^+ Ptch1^tm1Mps/Ptch1^tm1Mps Tg(Mt1-Ptch1)MT22Mps/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:3617156
cx37	Ptch1^tm1Mps/Ptch1^tm1Mps Tg(Mt1-Ptch1)MT22Mps/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:3617155
cx38	Hhip^tm1Amc/Hhip^tm1Amc Ptch1^tm1Mps/Ptch1^tm1Mps Tg(Mt1-Ptch1)MT22Mps/0	involves: 129S1/Sv * 129X1/SvJ * FVB	MGI:3617157
cx39	Gli2^tm1Alj/Gli2^tm1Alj Ptch1^tm1Mps/Ptch1^tm1Mps	involves: 129S1/Sv * 129X1/SvJ * Swiss Webster	MGI:3795856

Genotype
MGI:4461985

hm1

• Allelic Composition: Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

embryo

craniorachischisis ( J:297055 )

• open brain regions and extensive rostral malformations in E8.5 14-16 somite embryos

mortality/aging

embryonic lethality prior to organogenesis ( J:297055 )

• embryos are arrested stage E9-E9.5 with at least 14-16 somites

nervous system

craniorachischisis ( J:297055 )

• open brain regions and extensive rostral malformations in E8.5 14-16 somite embryos

Genotype
MGI:2655205

hm2

• Allelic Composition: Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

embryonic lethality, complete penetrance ( J:42441 )

• embryos die between E9.0 and E10.5

nervous system

open neural tube ( J:42441 )

• neural tube fails to close completely and is overgrown in the head folds, hindbrain, and spinal cord

cardiovascular system

abnormal heart development ( J:42441 )

• heart is not properly formed

embryo

open neural tube ( J:42441 )

• neural tube fails to close completely and is overgrown in the head folds, hindbrain, and spinal cord

Genotype
MGI:2676434

hm3

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

mortality/aging

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

• no homozygous embryos are recovered at E10.5 from intercrosses of double heterozygous Gli2, Ptc mice

Genotype
MGI:2675737

ht4

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

increased skin tumor incidence ( J:82653 )

• mutants develop small tumor foci/buds in the skin; these epithelial invaginations arise from both the hair follicle and the interfollicular epithelium

• tumor buds appear at the first postnatal anagen stage

increased rhabdomyosarcoma incidence ( J:114992 )

• low incidence in around 10% of mice

increased medulloblastoma incidence ( J:102702 , J:114992 , J:144811 )

• low incidence in around 10% of mice (J:114992)

• 15-20% of mice develop medulloblastomas (J:144811)

• tumors consist of small round cells with little cytoplasm and clearly demarcated borders (J:144811)

• 100% of immunocompromised hosts receiving >200,000 tumor cells will develop medulloblastomas with a mean latency of 49 days (J:144811)

• tumor cells expressing CD15⁺ have the characteristics of cancer stem cells including high rates of proliferation and ability to propagate the disease into immunocompromised hosts (J:144811)

integument

focal hair loss ( J:82653 )

• small foci of hair loss are observed, each one in association with epithelial invaginations

increased skin tumor incidence ( J:82653 )

• mutants develop small tumor foci/buds in the skin; these epithelial invaginations arise from both the hair follicle and the interfollicular epithelium

• tumor buds appear at the first postnatal anagen stage

nervous system

increased medulloblastoma incidence ( J:102702 , J:114992 , J:144811 )

• low incidence in around 10% of mice (J:114992)

• 15-20% of mice develop medulloblastomas (J:144811)

• tumors consist of small round cells with little cytoplasm and clearly demarcated borders (J:144811)

• 100% of immunocompromised hosts receiving >200,000 tumor cells will develop medulloblastomas with a mean latency of 49 days (J:144811)

• tumor cells expressing CD15⁺ have the characteristics of cancer stem cells including high rates of proliferation and ability to propagate the disease into immunocompromised hosts (J:144811)

muscle

increased rhabdomyosarcoma incidence ( J:114992 )

• low incidence in around 10% of mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:144811

Genotype
MGI:2173417

ht5

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:112118 )

• with increasing age (>12 months), Ptch1-heterozygous, Ptch2-sufficient mice are less healthy and die with no obvious tumor burden

decreased tumor-free survival time ( J:205254 )

• median survival of mutants that only develop medulloblastoma is 158 days

neoplasm

increased tumor incidence ( J:205254 )

• 14.3% of mutants develop other tumors, including hemangiosarcomas, intestinal tumors, rhabdomyosarcomas, and lymphomas

increased gastrointestinal tumor incidence ( J:205254 )

increased rhabdomyosarcoma incidence ( J:205254 )

increased lymphoma incidence ( J:205254 )

increased medulloblastoma incidence ( J:205254 )

• 42.8% of mutants develop medulloblastoma

• medulloblastomas are noninvasive and exhibit histologic patterns that mimic different phenotypes seen in human medulloblastoma, including classic biphasic phenotype and anaplastic variants

increased hemangiosarcoma incidence ( J:205254 )

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:205254 )

muscle

increased rhabdomyosarcoma incidence ( J:205254 )

nervous system

increased medulloblastoma incidence ( J:205254 )

• 42.8% of mutants develop medulloblastoma

• medulloblastomas are noninvasive and exhibit histologic patterns that mimic different phenotypes seen in human medulloblastoma, including classic biphasic phenotype and anaplastic variants

abnormal cerebellar molecular layer ( J:205254 )

• 1 month old cerebella show preneoplastic lesions in the outer molecular layer where progenitors within the external germinal layer previously resided, suggesting that medulloblastomas arise from granule neuron progenitors

Genotype
MGI:2177702

ht6

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

neoplasm

increased tumor incidence ( J:42441 )

• soft tissue tumors

increased medulloblastoma incidence ( J:42441 )

• tumors arise as early as 5 weeks of age and increase in severity and frequency with age

growth/size/body

increased body size ( J:42441 )

limbs/digits/tail

polydactyly ( J:42441 )

• seen in a small fraction of heterozygotes

syndactyly ( J:42441 )

• seen in a small fraction of heterozygotes

nervous system

increased medulloblastoma incidence ( J:42441 )

• tumors arise as early as 5 weeks of age and increase in severity and frequency with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nevoid basal cell carcinoma syndrome		DOID:2512	OMIM:PS109400	J:42441

Genotype
MGI:6259595

ht7

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J

neoplasm

increased basal cell carcinoma incidence ( J:58328 )

• mice over 9 months of age exhibit microscopic skin tumors that resemble human tumors of follicular origin and paw biopsies show demarcated stratum corneum defects or pits with underlying basal cell carcinoma-like tumors resembling the palmar pits of basal cell nevus syndrome patients

increased incidence of tumors by UV-induction ( J:58328 )

• mice exposed to chronic ultraviolet radiation show an increase in the number and size of basaloid cell tumors such that by 11 months of UV exposure, 86% of mice develop cutaneous tumors

• about 20% of UV-induced tumors are basal cell carcinoma or trichoblastomas, 30% are squamous cell carcinomas or keratoacanthomas, and 50% are fibrosarcomas or fibromas

• after 12 months of chronic UV exposure, all mice have tumors with features of basal cell carcinoma, with 44% classified as superficial, mostly interfollicular basaloid proliferations, 13% with features of nodular or infiltrating basal cell carcinoma, and 43% with features of trichoblastoma

• basal cell carcinoma and trichoblastoma show Ptch1 loss of heterozygosity

• 57% of mice receiving 11-12 months of UV exposure show invasive squamous cell carcinomas or keratoacanthomas compared to 25% of wild-type mice

increased incidence of tumors by ionizing radiation induction ( J:58328 )

• mice exposed to a single dose of ionizing radiation develop trichoblastoma-like tumors

• however, ionizing radiation treated mice do not develop fibrosarcomas or squamous cell carcinomas

integument

increased basal cell carcinoma incidence ( J:58328 )

• mice over 9 months of age exhibit microscopic skin tumors that resemble human tumors of follicular origin and paw biopsies show demarcated stratum corneum defects or pits with underlying basal cell carcinoma-like tumors resembling the palmar pits of basal cell nevus syndrome patients

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
basal cell carcinoma		DOID:2513		J:58328

Genotype
MGI:5544603

ht8

• Allelic Composition: Ptch1^dl/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/SvImJ * 129X1/SvJ * C57BL/6J

Skeletal abnormalities in Ptch1^dl/Ptch1^tm1Mps mice

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:204468 )

• some mice are dead upon collection at E18.5

craniofacial

abnormal craniofacial morphology ( J:204468 )

• mice with normal neural closure exhibit craniofacial defects similar to in Ptch1^dl homozygotes

abnormal lambdoid suture morphology ( J:204468 )

• absent

abnormal neurocranium morphology ( J:204468 )

• defects in the formation of endochondrial bones of the calvaria that are more severe than in Ptch1^dl homozygotes

small basisphenoid bone ( J:204468 )

• narrow

abnormal interparietal bone morphology ( J:204468 )

• fusion of the parietal and interparietal bones

abnormal parietal bone morphology ( J:204468 )

• fusion of the parietal and interparietal bones

alisphenoid bone hypoplasia ( J:204468 )

absent presphenoid bone ( J:204468 )

mandibular coronoid process hypoplasia ( J:204468 )

• underdeveloped

palatal shelf hypoplasia ( J:204468 )

• underdeveloped

limbs/digits/tail

preaxial polydactyly ( J:204468 )

• in all forelimbs and the majority of hindlimbs

syndactyly ( J:204468 )

• in all forelimbs and the majority of hindlimbs

kinked tail ( J:204468 )

nervous system

exencephaly ( J:204468 )

• in several mice at E18.5

digestive/alimentary system

palatal shelf hypoplasia ( J:204468 )

• underdeveloped

skeleton

abnormal lambdoid suture morphology ( J:204468 )

• absent

abnormal neurocranium morphology ( J:204468 )

• defects in the formation of endochondrial bones of the calvaria that are more severe than in Ptch1^dl homozygotes

small basisphenoid bone ( J:204468 )

• narrow

abnormal interparietal bone morphology ( J:204468 )

• fusion of the parietal and interparietal bones

abnormal parietal bone morphology ( J:204468 )

• fusion of the parietal and interparietal bones

alisphenoid bone hypoplasia ( J:204468 )

absent presphenoid bone ( J:204468 )

mandibular coronoid process hypoplasia ( J:204468 )

• underdeveloped

scapular bone foramen ( J:204468 )

• in 5 of 10 mice

abnormal sternum morphology ( J:204468 )

• disorganized and thicker than in control mice with more ossification

growth/size/body

palatal shelf hypoplasia ( J:204468 )

• underdeveloped

Genotype
MGI:3831343

cn9

• Allelic Composition: Brca2^tm1Brn/Brca2^tm1Brn; Ptch1^tm1Mps/Ptch1⁺; Trp53^tm1Tyj/Trp53^tm1Tyj; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

neoplasm

increased medulloblastoma incidence ( J:144617 )

• 100% of mice develop medulloblastoma beginning at 5 weeks

nervous system

increased medulloblastoma incidence ( J:144617 )

• 100% of mice develop medulloblastoma beginning at 5 weeks

Genotype
MGI:3831342

cn10

• Allelic Composition: Brca2^tm1Brn/Brca2^tm1Brn; Ptch1^tm1Mps/Ptch1⁺; Trp53^tm1Tyj/Trp53⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129 * C57BL/6 * SJL

neoplasm

increased medulloblastoma incidence ( J:144617 )

• 100% of mice develop medulloblastoma beginning at 10 weeks

nervous system

increased medulloblastoma incidence ( J:144617 )

• 100% of mice develop medulloblastoma beginning at 10 weeks

Genotype
MGI:5317025

cn11

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Tg(Atoh1-sb11)1Mtay/0; TgTn(sb-T2/Onc3)12740Njen/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6J * ICR

neoplasm

increased medulloblastoma incidence ( J:181542 )

• 271 of 279 mice develop medulloblastoma compared with 54 of 139 control mice with decreased latency (2.5 months compared with 8 months)

nervous system

increased medulloblastoma incidence ( J:181542 )

• 271 of 279 mice develop medulloblastoma compared with 54 of 139 control mice with decreased latency (2.5 months compared with 8 months)

Genotype
MGI:3759458

cx12

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129 * 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:125534 )

• mice die around 2 months of age compared to Trp53^tm1Tyj that survive to 5 months

neoplasm

increased rhabdomyosarcoma incidence ( J:125534 )

• 3 of 16 mice develop rhabdomyosarcoma

increased medulloblastoma incidence ( J:125534 )

• 15 of 16 mice develop medulloblastomas that express TUBB3 and GFAP and exhibit increased apoptosis

muscle

increased rhabdomyosarcoma incidence ( J:125534 )

• 3 of 16 mice develop rhabdomyosarcoma

nervous system

increased medulloblastoma incidence ( J:125534 )

• 15 of 16 mice develop medulloblastomas that express TUBB3 and GFAP and exhibit increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:67452

Genotype
MGI:6514750

cx13

• Allelic Composition: Chmp1a^Gt(XC472)Byg/Chmp1a^Gt(XC472)Byg; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

nervous system

nervous system phenotype ( J:271138 )

N • at E18.5/P0, brain weight is not significantly different from that in controls, indicating that the microcephaly of Chmp1a^Gt(XC472)Byg homozygotes (reflecting reduced Shh function) is reversed

Genotype
MGI:3710324

cx14

• Allelic Composition: Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

nervous system

abnormal neuron differentiation ( J:102702 )

• granule neuronal precursors (GNPs) show enhanced proliferation after stimulation with Shh in culture relative to Ptch1 heterozygous, Cdkn2c wild-type cerebellar cells isolated at P10

increased medulloblastoma incidence ( J:102702 )

• mice exhibit earlier onset of tumor formation with greatly increased incidence compared to Ptch1 heterozygotes

neoplasm

increased medulloblastoma incidence ( J:102702 )

• mice exhibit earlier onset of tumor formation with greatly increased incidence compared to Ptch1 heterozygotes

cellular

abnormal neuron differentiation ( J:102702 )

• granule neuronal precursors (GNPs) show enhanced proliferation after stimulation with Shh in culture relative to Ptch1 heterozygous, Cdkn2c wild-type cerebellar cells isolated at P10

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:102702

Genotype
MGI:3690370

cx15

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Ptch2^tm1Pmc/Ptch2⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6

neoplasm

neoplasm ( J:112118 )

N • mice show no increase in tumor incidence compared to Ptch1/Trp53 double null mice

Genotype
MGI:5544755

cx16

• Allelic Composition: Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:205254 )

• median survival of mutants that only develop medulloblastoma is 114 days

neoplasm

increased tumor incidence ( J:205254 )

• 30% of mutants develop other tumors, including hemangiosarcomas, intestinal tumors, rhabdomyosarcomas, and lymphomas

• however, no pituitary tumors are seen

increased gastrointestinal tumor incidence ( J:205254 )

increased rhabdomyosarcoma incidence ( J:205254 )

increased lymphoma incidence ( J:205254 )

increased medulloblastoma incidence ( J:205254 )

• 66.7% of mutants develop medulloblastoma

• formation of medulloblastoma formation is accelerated compared to single Ptch1 heterozygotes or double heterozygotes

• medulloblastomas are less differentiated and more invasive than medulloblastomas from single Ptch1 heterozygotes

increased hemangiosarcoma incidence ( J:205254 )

nervous system

increased medulloblastoma incidence ( J:205254 )

• 66.7% of mutants develop medulloblastoma

• formation of medulloblastoma formation is accelerated compared to single Ptch1 heterozygotes or double heterozygotes

• medulloblastomas are less differentiated and more invasive than medulloblastomas from single Ptch1 heterozygotes

hydrocephaly ( J:205254 )

• fraction of mutants develop hydrocephalus unrelated to tumor formation

abnormal cerebellar molecular layer ( J:205254 )

• 1 month old cerebella show preneoplastic lesions in the outer molecular layer where progenitors within the external germinal layer previously resided, suggesting that medulloblastomas arise from granule neuron progenitors

muscle

increased rhabdomyosarcoma incidence ( J:205254 )

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:205254 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:205254

Genotype
MGI:5544754

cx17

• Allelic Composition: Cdkn1b^tm1Mlf/Cdkn1b⁺; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:205254 )

• median survival of mutants that only develop medulloblastoma is 127 days

neoplasm

increased tumor incidence ( J:205254 )

• 11.8% of mutants develop other tumors, including hemangiosarcomas, intestinal tumors, rhabdomyosarcomas, and lymphomas

increased gastrointestinal tumor incidence ( J:205254 )

increased rhabdomyosarcoma incidence ( J:205254 )

increased lymphoma incidence ( J:205254 )

increased medulloblastoma incidence ( J:205254 )

• 59.7% of mutants develop medulloblastoma

• medulloblastomas are less differentiated and more invasive than medulloblastomas from single Ptch1 heterozygotes, sometimes penetrating the white matter and sometimes obliterating the normal contours of the cerebellar lobes

increased hemangiosarcoma incidence ( J:205254 )

nervous system

increased medulloblastoma incidence ( J:205254 )

• 59.7% of mutants develop medulloblastoma

• medulloblastomas are less differentiated and more invasive than medulloblastomas from single Ptch1 heterozygotes, sometimes penetrating the white matter and sometimes obliterating the normal contours of the cerebellar lobes

hydrocephaly ( J:205254 )

• fraction of mutants develop hydrocephalus unrelated to tumor formation

abnormal cerebellar molecular layer ( J:205254 )

• 1 month old cerebella show preneoplastic lesions in the outer molecular layer where progenitors within the external germinal layer previously resided, suggesting that medulloblastomas arise from granule neuron progenitors

muscle

increased rhabdomyosarcoma incidence ( J:205254 )

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:205254 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:205254

Genotype
MGI:5432799

cx18

• Allelic Composition: Gli2^tm3.1Blnw/Gli2^tm3.1Blnw; Ptch1^tm1Mps/?
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H * C57BL/6

embryo

abnormal neural tube morphology ( J:186503 )

• at E10.5, Patch1-lacZ expression is slightly increased and dorsally expanded in the neural tube compared to in wild-type mice

nervous system

abnormal neural tube morphology ( J:186503 )

• at E10.5, Patch1-lacZ expression is slightly increased and dorsally expanded in the neural tube compared to in wild-type mice

Genotype
MGI:3665561

cx19

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Tg(Shh)#Dje/0
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * Swiss Webster

nervous system

abnormal cerebellum morphology ( J:108507 )

• cerebellum is larger than in Tg(Shh)#Dje-expressing mice

abnormal cerebellum development ( J:108507 )

• mutants have an extra lobule on rostral face of lobule VI

abnormal cerebellar foliation ( J:108507 )

• foliation is not enhanced compared to non transgenic conditional Gli2 knockouts

Genotype
MGI:2675747

cx20

• Allelic Composition: Hhip^tm1Amc/Hhip^tm1Amc; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

embryonic lethality, complete penetrance ( J:85472 )

• accelerated lethality before E13

growth/size/body

increased embryo size ( J:94269 )

• about 56% of embryos

respiratory system

small lung ( J:85472 )

• much smaller lungs

abnormal pulmonary alveolar duct morphology ( J:94269 )

• branching pattern defect much more severe

nervous system

abnormal neural tube morphology ( J:94269 )

• enlarged neural tube

• ventricular zone grossly normal

incomplete rostral neuropore closure ( J:94269 )

• normal sized embryos with "open brains"

• moderate overgrowth in some cases

increased neuronal precursor cell number ( J:94269 )

• general expansion of neuronal precursor populations

digestive/alimentary system

abnormal stomach glandular epithelium morphology ( J:85472 )

• very reduced in thickness

endocrine/exocrine glands

abnormal pancreas development ( J:85472 )

• at E12.5, pancreas morphogenesis and cell differentiation are severely impaired

abnormal branching involved in pancreas development ( J:85472 )

• impaired branching of pancreatic epithelium into surrounding mesenchyme

• pancreatic epithelium significantly reduced

embryo

increased embryo size ( J:94269 )

• about 56% of embryos

abnormal neural tube morphology ( J:94269 )

• enlarged neural tube

• ventricular zone grossly normal

incomplete rostral neuropore closure ( J:94269 )

• normal sized embryos with "open brains"

• moderate overgrowth in some cases

Genotype
MGI:5447987

cx21

• Allelic Composition: Hhat^{Tg(TFAP2A-cre)1Will}/Hhat⁺; Ptch1^tm1Mps/Ptch1⁺
• 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 Ptch1.

Genotype
MGI:3052724

cx22

• Allelic Composition: Disp1^tm1Amc/Disp1^tm1Amc; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

normal phenotype

no abnormal phenotype detected ( J:92058 )

• viable fertile, and outwardly normal

nervous system

nervous system phenotype ( J:92058 )

N • normal floor plate and progenitor/precursor neuron patterning

Genotype
MGI:3783757

cx23

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Shh^tm6Amc/Shh^tm6Amc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

normal phenotype

no abnormal phenotype detected ( J:132152 )

• significantly normalized the size of each neural progenitor domains and the gross phenotype of Shh^tm6Amc/Shh^tm6Amc homozygous mice

• authors did not mention whether the prenatal lethality phenotype found in Shh^tm6Amc/Shh^tm6Amc homozygous mice was rescued or not

Genotype
MGI:5319221

cx24

• Allelic Composition: Mtss1^tm1Pla/Mtss1^tm1Pla; Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

embryonic lethality, complete penetrance ( J:182970 )

• embryonic lethality observed in Ptch1^tm1Mps homozygotes is not rescued

Genotype
MGI:3795858

cx25

• Allelic Composition: Gli1^tm1Alj/Gli1^tm1Alj; Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss * Swiss Webster

mortality/aging

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

• no mutants are recovered after E9.5

Genotype
MGI:5803873

cx26

• Allelic Composition: Disp1^icb/Disp1^icb; Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J

mortality/aging

embryonic lethality, complete penetrance ( J:79027 )

• embryos arrested at E9.0-9.5

nervous system

abnormal neural tube morphology ( J:79027 )

• neural tube was ventralized

open neural tube ( J:79027 )

embryo

abnormal neural tube morphology ( J:79027 )

• neural tube was ventralized

open neural tube ( J:79027 )

growth/size/body

abnormal head morphology ( J:79027 )

• heads of the embryos appeared truncated

Genotype
MGI:5433092

cx27

• Allelic Composition: Ptch1^tm1Mps/Ptch1^tm1Mps; Tmem107^schlei/Tmem107^schlei
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3HeB/FeJ * C57BL/6J

nervous system

abnormal neural tube closure ( J:186552 )

• neural tube closure defects observed in Ptch1^tm1Mps homozygotes are partially rescued

exencephaly ( J:186552 )

growth/size/body

decreased embryo size ( J:186552 )

• reduced embryo size observed in Ptch1^tm1Mps homozygotes is partially rescued

abnormal head morphology ( J:186552 )

• head formation defects observed in Ptch1^tm1Mps homozygotes are partially rescued

embryo

decreased embryo size ( J:186552 )

• reduced embryo size observed in Ptch1^tm1Mps homozygotes is partially rescued

abnormal neural tube closure ( J:186552 )

• neural tube closure defects observed in Ptch1^tm1Mps homozygotes are partially rescued

Genotype
MGI:3690366

cx28

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Ptch2^tm1Pmc/Ptch2⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

neoplasm

increased testicular teratoma incidence ( J:112118 )

♂ • 2/54 males develop testicular teratomas

increased basal cell carcinoma incidence ( J:112118 )

• frequency is greater (3/63) compared to Ptch1-deficient mice (1/62)

increased rhabdomyosarcoma incidence ( J:112118 )

• incidence is increased in frequency

decreased tumor latency ( J:112118 )

• 50% develop tumors by 5 months of age, compared to ~15% of Ptch1-heterozygous, Ptch2-sufficient mice develop tumors by 12 months of age

cardiovascular system

telangiectasia ( J:112118 )

• subcutaneous telangiectasia is observed in 2% of mice

digestive/alimentary system

abnormal intestine morphology ( J:112118 )

• ~19% of mice display intestinal serosal angiectasis

muscle

telangiectasia ( J:112118 )

• subcutaneous telangiectasia is observed in 2% of mice

increased rhabdomyosarcoma incidence ( J:112118 )

• incidence is increased in frequency

integument

increased basal cell carcinoma incidence ( J:112118 )

• frequency is greater (3/63) compared to Ptch1-deficient mice (1/62)

endocrine/exocrine glands

increased testicular teratoma incidence ( J:112118 )

♂ • 2/54 males develop testicular teratomas

reproductive system

increased testicular teratoma incidence ( J:112118 )

♂ • 2/54 males develop testicular teratomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:112118

Genotype
MGI:7432575

cx29

• Allelic Composition: Ihh^tm1Amc/Ihh^tm1Amc; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

craniofacial

abnormal palatal shelf bone ossification ( J:182649 )

• at E16.5 and E18.5, Xgal staining is reduced in the palate, predominantly at the ossification fronts of the palatine bone, indicating reduced ossification of the secondary hard palate

digestive/alimentary system

abnormal palatal shelf bone ossification ( J:182649 )

• at E16.5 and E18.5, Xgal staining is reduced in the palate, predominantly at the ossification fronts of the palatine bone, indicating reduced ossification of the secondary hard palate

growth/size/body

abnormal palatal shelf bone ossification ( J:182649 )

• at E16.5 and E18.5, Xgal staining is reduced in the palate, predominantly at the ossification fronts of the palatine bone, indicating reduced ossification of the secondary hard palate

Genotype
MGI:3690367

cx30

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Ptch2^tm1Pmc/Ptch2^tm1Pmc
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

neoplasm

increased tumor incidence ( J:112118 )

• increased tumorigenesis is readily apparent in 6th-generation compound mutants

increased basal cell carcinoma incidence ( J:112118 )

• frequency is greater (5/97) compared to Ptch1-deficient mice (1/62)

increased rhabdomyosarcoma incidence ( J:112118 )

• incidence is increased in frequency

increased medulloblastoma incidence ( J:112118 )

• occur with higher frequency

decreased tumor latency ( J:112118 )

• 50% develop tumors by 10 months of age, compared to ~15% of Ptch1-heterozygous, Ptch2-sufficient mice develop tumors by 12 months of age

digestive/alimentary system

abnormal intestine morphology ( J:112118 )

• ~18% of mice display intestinal serosal angiectasis

integument

increased basal cell carcinoma incidence ( J:112118 )

• frequency is greater (5/97) compared to Ptch1-deficient mice (1/62)

nervous system

increased medulloblastoma incidence ( J:112118 )

• occur with higher frequency

muscle

increased rhabdomyosarcoma incidence ( J:112118 )

• incidence is increased in frequency

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:112118

Genotype
MGI:5544756

cx31

• Allelic Composition: Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd; Ptch1^tm1Mps/Ptch1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

neoplasm

increased medulloblastoma incidence ( J:205254 )

• 7 of 11 mutants exhibit invasive medulloblastoma

nervous system

increased medulloblastoma incidence ( J:205254 )

• 7 of 11 mutants exhibit invasive medulloblastoma

abnormal cerebellar molecular layer ( J:205254 )

• 1 month old cerebella show preneoplastic lesions in the outer molecular layer where progenitors within the external germinal layer previously resided, suggesting that medulloblastomas arise from granule neuron progenitors

Genotype
MGI:3836962

cx32

• Allelic Composition: Ptch1^tm1Mps/Ptch1⁺; Tg(Atoh1-GFP)1Jejo/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

neoplasm

increased medulloblastoma incidence ( J:144811 )

• 80-95% of tumor cells express GFP

• GFP⁺ tumor cells but not GFP^- are able to propagate tumors into immunocompromised hosts

nervous system

increased medulloblastoma incidence ( J:144811 )

• 80-95% of tumor cells express GFP

• GFP⁺ tumor cells but not GFP^- are able to propagate tumors into immunocompromised hosts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:144811

Genotype
MGI:5558105

cx33

• Allelic Composition: Ptch1^tm1Mps/Ptch1^tm1Mps; Wdpcp^cys40/Wdpcp^cys40
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

embryo

abnormal embryo development ( J:205269 )

• double mutants show better axial development, more robust growth and more normal head and heart development compared to mice homozygous for Ptch1^tm1Mps alone

Genotype
MGI:3624275

cx34

• Allelic Composition: Dync2h1^lln/Dync2h1^lln; Ptch1^tm1Mps/Ptch1^tm1Mps
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:100466 )

• double mutants die around E12.5

Genotype
MGI:4355990

cx35

• Allelic Composition: Kif7^maki/Kif7^maki; Ptch1^tm1Mps/Ptch1^tm1Mps; Tg(Hlxb9-GFP)1Tmj/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:151965 )

• compound mutants develop until E10.5, unlike Ptch1 single mutants that arrest at about E9.0

nervous system

abnormal neural tube morphology ( J:151965 )

• ventral cell types are expanded to encompass about 3/4 of the neural plate

• this expansion is less than that seen in Ptch1 single mutants

embryo

abnormal neural tube morphology ( J:151965 )

• ventral cell types are expanded to encompass about 3/4 of the neural plate

• this expansion is less than that seen in Ptch1 single mutants

Genotype
MGI:3617156

cx36

• Allelic Composition: Hhip^tm1Amc/Hhip⁺; Ptch1^tm1Mps/Ptch1^tm1Mps; Tg(Mt1-Ptch1)MT22Mps/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

nervous system

abnormal neural tube morphology ( J:94269 )

spina bifida ( J:94269 )

• or exencephaly present

exencephaly ( J:94269 )

• or spina bifida present

abnormal neuronal precursor cell number ( J:94269 )

• ventral neuronal precursor population expanded considerably

craniofacial

small first pharyngeal arch ( J:94269 )

• hyperplastic first branchial arch

embryo

small first pharyngeal arch ( J:94269 )

• hyperplastic first branchial arch

abnormal neural tube morphology ( J:94269 )

spina bifida ( J:94269 )

• or exencephaly present

Genotype
MGI:3617155

cx37

• Allelic Composition: Ptch1^tm1Mps/Ptch1^tm1Mps; Tg(Mt1-Ptch1)MT22Mps/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

nervous system

abnormal neural tube morphology ( J:94269 )

abnormal diencephalon morphology ( J:94269 )

• look normal at E10.5 except for a slight overgrowth in the diencephalon

abnormal neuronal precursor cell number ( J:94269 )

• ventral neuronal precursor population 2X controls, other precursor populations normal

embryo

abnormal neural tube morphology ( J:94269 )

Genotype
MGI:3617157

cx38

• Allelic Composition: Hhip^tm1Amc/Hhip^tm1Amc; Ptch1^tm1Mps/Ptch1^tm1Mps; Tg(Mt1-Ptch1)MT22Mps/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:94269 )

• half are dead at E10.5

nervous system

abnormal neural tube morphology ( J:94269 )

• ventral neuronal precursor population expanded and dorsal precursors decreased

enlarged floor plate ( J:94269 )

• 3X size of controls

incomplete rostral neuropore closure ( J:94269 )

• brain entirely open

abnormal neuronal precursor cell number ( J:94269 )

• entral neuronal precursor population expanded and dorsal precursors decreased

craniofacial

enlarged first pharyngeal arch ( J:94269 )

• first branchial arch considerably enlarged

vision/eye

anophthalmia ( J:94269 )

embryo

enlarged first pharyngeal arch ( J:94269 )

• first branchial arch considerably enlarged

abnormal neural tube morphology ( J:94269 )

• ventral neuronal precursor population expanded and dorsal precursors decreased

enlarged floor plate ( J:94269 )

• 3X size of controls

incomplete rostral neuropore closure ( J:94269 )

• brain entirely open

Genotype
MGI:3795856

cx39

• 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