Phenotypes associated with this allele

• Allele Symbol: Ptch1^tm1Zim
• Allele Name: targeted mutation 1, Andreas Zimmer
• Allele ID: MGI:1857935
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptch1^tm1Zim/Ptch1^tm1Zim	involves: 129	MGI:4837635
ht2	Ptch1^tm1Zim/Ptch1^+	either: (involves: 129 * C57BL/6) or (involves: 129 * CD-1)	MGI:2679475
ht3	Ptch1^tm1Zim/Ptch1^+	involves: 129 * CD-1	MGI:3040327
ht4	Ptch1^dl/Ptch1^tm1Zim	involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J	MGI:5544605
cx5	Ptch1^tm1Zim/Ptch1^tm1Zim Stil^tm1Mku/Stil^tm1Mku	involves: 129	MGI:3036865
cx6	Parms1^C57BL/6NCrl/Parms1^C57BL/6NCrl Ptch1^tm1Zim/Ptch1^+	involves: 129/Sv * BALB/cByJ * C57BL/6NCrl	MGI:3522459
cx7	Parms1^BALB/cByJ/Parms1^C57BL/6NCrl Ptch1^tm1Zim/Ptch1^+	involves: 129/Sv * BALB/cByJ * C57BL/6NCrl	MGI:3522460
cx8	Gpr37l1^tm1.2Gtva/Gpr37l1^tm1.2Gtva Ptch1^tm1Zim/Ptch1^+	STOCK Gpr37l1^tm1.2Gtva Ptch1^tm1Zim/Cnrm	MGI:6429905

Genotype
MGI:4837635

hm1

• Allelic Composition: Ptch1^tm1Zim/Ptch1^tm1Zim
• Genetic Background: involves: 129

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:47421 )

• die at E9

embryo

abnormal neural tube closure ( J:47421 )

• neural folds fail to close

nervous system

abnormal neural tube closure ( J:47421 )

• neural folds fail to close

Genotype
MGI:2679475

ht2

• Allelic Composition: Ptch1^tm1Zim/Ptch1⁺
• Genetic Background: either: (involves: 129 * C57BL/6) or (involves: 129 * CD-1)

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:47421 )

• Background Sensitivity: on CD-1 background, 7% of mutants die and/or are resorbed on E16.5 while on a C57BL/6 background, 22% of mutants die on E16.5

muscle

increased rhabdomyosarcoma incidence ( J:47421 )

• Background Sensitivity: 9% of young mutants aged 6-13 weeks exhibit rhabdomyosarcoma on a CD-1 background

• Background Sensitivity: incidence of rhabdomyosarcoma is lower on the C57BL/6 background than on the CD-1 background, with only 1 of 53 showing this phenotype

• tumors generally involve the skeletal muscle of the rear thigh, lumbar region or abdominal wall

• tumors are unencapsulated and neoplastic cells invade the adjacent muscle and fat

craniofacial

mandibular cyst ( J:47421 )

• mice exhibit a mandibular cyst lined by squamous epithelium adjacent to a tooth root

embryo

incomplete rostral neuropore closure ( J:47421 )

• 2 of 44 mutants on a CD-1 background at E16.5 exhibit failure of anterior neural tube closure

growth/size/body

mandibular cyst ( J:47421 )

• mice exhibit a mandibular cyst lined by squamous epithelium adjacent to a tooth root

dermal cyst ( J:47421 )

• dermal cyst is lined with keratinizing epithelium and filled with hair shafts

increased body size ( J:47421 )

• generalized overgrowth by 20% at 6-8 weeks of age

increased fetal size ( J:47421 )

• 12% increase in body size at E16.5

limbs/digits/tail

polydactyly ( J:47421 )

preaxial polydactyly ( J:47421 )

nervous system

incomplete rostral neuropore closure ( J:47421 )

• 2 of 44 mutants on a CD-1 background at E16.5 exhibit failure of anterior neural tube closure

increased medulloblastoma incidence ( J:47421 )

• develop medulloblastomas

exencephaly ( J:47421 )

• 2 of 44 mutants on a CD-1 background at E16.5 exhibit failure of anterior neural tube closure leading to exencephaly

skeleton

mandibular cyst ( J:47421 )

• mice exhibit a mandibular cyst lined by squamous epithelium adjacent to a tooth root

abnormal rib morphology ( J:47421 )

• rib anomalies

decreased rib number ( J:47421 )

• missing rib

neoplasm

increased rhabdomyosarcoma incidence ( J:47421 )

• Background Sensitivity: 9% of young mutants aged 6-13 weeks exhibit rhabdomyosarcoma on a CD-1 background

• Background Sensitivity: incidence of rhabdomyosarcoma is lower on the C57BL/6 background than on the CD-1 background, with only 1 of 53 showing this phenotype

• tumors generally involve the skeletal muscle of the rear thigh, lumbar region or abdominal wall

• tumors are unencapsulated and neoplastic cells invade the adjacent muscle and fat

increased medulloblastoma incidence ( J:47421 )

• develop medulloblastomas

increased incidence of tumors by ionizing radiation induction ( J:47421 )

• embryos on the CD-1 background exhibit increased sensitivity to ionizing radiation than wild-type embryos, with a 4.1 times higher frequency of defects such as micropthalmia, anopthalmia, exencephaly, polydactyly or syndactyly

integument

dermal cyst ( J:47421 )

• dermal cyst is lined with keratinizing epithelium and filled with hair shafts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nevoid basal cell carcinoma syndrome		DOID:2512	OMIM:PS109400	J:47421

Genotype
MGI:3040327

ht3

• Allelic Composition: Ptch1^tm1Zim/Ptch1⁺
• Genetic Background: involves: 129 * CD-1

mortality/aging

increased mortality induced by ionizing radiation ( J:79666 )

• newborns irradiated with X-rays develop increased incidence of medulloblastoma and exhibit a higher mortality compared to irradiated wild-type mice or unirradiated heterozygotes, such that by 38 weeks of age, 33% of wild-type die versus 90% of mutants

• irradiated mutants die predominately from medulloblastomas while wild-type mice die from thymic lymphomas

neoplasm

increased medulloblastoma incidence ( J:79666 , J:165388 )

• spontaneous medulloblastoma incidence of 7.7% (J:79666)

• newborns, but not adults, show increased susceptibility to medulloblastoma formation following X-ray irradiation, with 74.5% incidence in mutants compared to 19.2% incidence in unirradiated mutants and 30.4% incidence in irradiated wild-type mice (J:79666)

• tumors show loss of the wild-type allele (J:79666)

• susceptibility of radiation-induced medulloblastoma development is increased in females that are ovariectomized compared to non-ovariectomized females (J:165388)

• estrogen replacement reduces this susceptibility back to levels seen in non-ovariectomized females (J:165388)

increased incidence of tumors by ionizing radiation induction ( J:79666 , J:165388 )

• newborns, but not adults, show increased susceptibility to medulloblastoma formation following X-ray irradiation, with 51% incidence compared to 7% in non-irradiated mutants (J:79666)

• susceptibility of radiation-induced medulloblastoma development is increased in females that are ovariectomized compared to non-ovariectomized females (J:165388)

homeostasis/metabolism

increased mortality induced by ionizing radiation ( J:79666 )

• newborns irradiated with X-rays develop increased incidence of medulloblastoma and exhibit a higher mortality compared to irradiated wild-type mice or unirradiated heterozygotes, such that by 38 weeks of age, 33% of wild-type die versus 90% of mutants

• irradiated mutants die predominately from medulloblastomas while wild-type mice die from thymic lymphomas

nervous system

increased medulloblastoma incidence ( J:79666 , J:165388 )

• spontaneous medulloblastoma incidence of 7.7% (J:79666)

• newborns, but not adults, show increased susceptibility to medulloblastoma formation following X-ray irradiation, with 74.5% incidence in mutants compared to 19.2% incidence in unirradiated mutants and 30.4% incidence in irradiated wild-type mice (J:79666)

• tumors show loss of the wild-type allele (J:79666)

• susceptibility of radiation-induced medulloblastoma development is increased in females that are ovariectomized compared to non-ovariectomized females (J:165388)

• estrogen replacement reduces this susceptibility back to levels seen in non-ovariectomized females (J:165388)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:79666

Genotype
MGI:5544605

ht4

• Allelic Composition: Ptch1^dl/Ptch1^tm1Zim
• Genetic Background: involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J

Kinked tail, omphalocele, and abnormal skull shape in Ptch1^dl/Ptch1^tm1Zim embryos

craniofacial

domed cranium ( J:204468 )

• domed skull with distinct angular separation from the snout at E18.5

growth/size/body

omphalocele ( J:204468 )

• small at E18.5

abnormal head morphology ( J:204468 )

• domed skull with distinct angular separation from the snout at E18.5

increased fetal size ( J:204468 )

• at E18.5

limbs/digits/tail

kinked tail ( J:204468 )

• at E18.5

skeleton

domed cranium ( J:204468 )

• domed skull with distinct angular separation from the snout at E18.5

Genotype
MGI:3036865

cx5

• Allelic Composition: Ptch1^tm1Zim/Ptch1^tm1Zim; Stil^tm1Mku/Stil^tm1Mku
• Genetic Background: involves: 129

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:72500 )

• homozygotes die around E9.5

• phenotype is identical to that of mice homozygous only for Sil^tm1Mku

cellular

abnormal apoptosis ( J:72500 )

• extensive apoptosis in the dorsal midline in the neural folds and in somites

• phenotype is identical to that of mice homozygous only for Sil^tm1Mku

nervous system

holoprosencephaly ( J:72500 )

• lack of any midline separation at the anterior end of the cranial neural folds

• phenotype is identical to that of mice homozygous only for Sil^tm1Mku

Genotype
MGI:3522459

cx6

• Allelic Composition: Parms1^C57BL/6NCrl/Parms1^C57BL/6NCrl; Ptch1^tm1Zim/Ptch1⁺
• Genetic Background: involves: 129/Sv * BALB/cByJ * C57BL/6NCrl

neoplasm

increased rhabdomyosarcoma incidence ( J:93364 )

• resistance to rhabdomyosarcoma development (longer latency)

muscle

increased rhabdomyosarcoma incidence ( J:93364 )

• resistance to rhabdomyosarcoma development (longer latency)

Genotype
MGI:3522460

cx7

• Allelic Composition: Parms1^BALB/cByJ/Parms1^C57BL/6NCrl; Ptch1^tm1Zim/Ptch1⁺
• Genetic Background: involves: 129/Sv * BALB/cByJ * C57BL/6NCrl

neoplasm

increased rhabdomyosarcoma incidence ( J:93364 )

• susceptibility to rhabdomyosarcoma development (shorter latency)

muscle

increased rhabdomyosarcoma incidence ( J:93364 )

• susceptibility to rhabdomyosarcoma development (shorter latency)

Genotype
MGI:6429905

cx8

• Allelic Composition: Gpr37l1^tm1.2Gtva/Gpr37l1^tm1.2Gtva; Ptch1^tm1Zim/Ptch1⁺
• Genetic Background: STOCK Gpr37l1^tm1.2Gtva Ptch1^tm1Zim/Cnrm

neoplasm

increased tumor incidence ( J:272049 )

• increased noninvasive tumors compared to in Ptch1^tm1Zim heterozygotes

increased medulloblastoma incidence ( J:272049 )

• mice develop medulloblastomas at a reduced incidence and delayed onset with reduced hydrocephalus compared with Ptch1^tm1Zim heterozygotes

increased tumor latency ( J:272049 )

• compared to in Ptch1^tm1Zim heterozygotes

nervous system

decreased cerebellar granule cell precursor proliferation ( J:272049 )

• compared to in Ptch1^tm1Zim heterozygotes

increased medulloblastoma incidence ( J:272049 )

• mice develop medulloblastomas at a reduced incidence and delayed onset with reduced hydrocephalus compared with Ptch1^tm1Zim heterozygotes

hydrocephaly ( J:272049 )

• reduced compared to in Ptch1^tm1Zim heterozygotes

cellular

decreased cerebellar granule cell precursor proliferation ( J:272049 )

• compared to in Ptch1^tm1Zim heterozygotes