Phenotypes associated with this allele

• Allele Symbol: Cdh1^tm1Jjon
• Allele Name: targeted mutation 1, Jos Jonkers
• Allele ID: MGI:3693661
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cdh1^tm1Jjon/Cdh1^tm1Jjon Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre)8Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3695271
cn2	Cdh1^tm1Jjon/Cdh1^tm1Jjon Trp53^tm1Brn/Trp53^+ Tg(KRT14-cre)8Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3695272
cn3	Cdh1^tm1Jjon/Cdh1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre)8Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3695273
cn4	Cdh1^tm1Jjon/Cdh1^tm1Jjon Tg(KRT14-cre)8Brn/0	involves: 129P2/OlaHsd * FVB/N	MGI:3695274
cn5	Cdh1^tm1Jjon/Cdh1^tm1Jjon Tg(Wap-cre)51Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:6296605
cn6	Cdh1^tm1Jjon/Cdh1^tm1Jjon Trp53^tm1Brn/Trp53^tm1Brn Tg(Wap-cre)51Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:6296606
cn7	Cdh1^tm1Jjon/Cdh1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Wap-cre)51Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:6296608
cn8	Cdh1^tm1Jjon/Cdh1^tm1Jjon Trp53^tm1Brn/Trp53^+ Tg(Wap-cre)51Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:6296609

Genotype
MGI:3695271

cn1

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT14-cre)8Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

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

neoplasm

abnormal tumor vascularization ( J:116152 )

• mammary tumors show large numbers of uniformly distributed blood vessels

• a 3-fold increase in vasculature is observed compared to mutants homozygous for Cdh1 deletion and heterozygous for Trp53 deletion

increased mammary adenocarcinoma incidence ( J:116152 )

• develop at accelerated rate compared to single conditional Trp53 mutant females

• multiple tumors develop with median latency of 214 days

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth

increased skin tumor incidence ( J:116152 )

• develop at accelerated rate compared to single conditional Trp53 mutant females

• multiple tumors develop with median latency of 214 days

• often show phenotypic change from expansive to invasive growth

• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis

increased metastatic potential ( J:116152 )

• in females presenting carcinomas ~1 cm in diameter, majority of tumors show extensive local invasion with ~50% demonstrating metastasis to draining and distant lymph nodes

• minority of animals show dissociated or loosely clustered lobulocarcinoma (ILC) cells in lungs, liver, gastrointestinal and urogenital tracts, and pancreas, or diffusely throughout peritoneal cavity

cardiovascular system

abnormal tumor vascularization ( J:116152 )

• mammary tumors show large numbers of uniformly distributed blood vessels

• a 3-fold increase in vasculature is observed compared to mutants homozygous for Cdh1 deletion and heterozygous for Trp53 deletion

integument

increased mammary adenocarcinoma incidence ( J:116152 )

• develop at accelerated rate compared to single conditional Trp53 mutant females

• multiple tumors develop with median latency of 214 days

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth

increased skin tumor incidence ( J:116152 )

• develop at accelerated rate compared to single conditional Trp53 mutant females

• multiple tumors develop with median latency of 214 days

• often show phenotypic change from expansive to invasive growth

• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:116152 )

• develop at accelerated rate compared to single conditional Trp53 mutant females

• multiple tumors develop with median latency of 214 days

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomorphic nuclei; these display both expansive and invasive growth

Genotype
MGI:3695272

cn2

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Trp53^tm1Brn/Trp53⁺; Tg(KRT14-cre)8Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

abnormal tumor vascularization ( J:116152 )

• mammary tumors show less vascularization, especially in periphery compared to double conditional null mice

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth

• massive central necrosis is observed

increased skin tumor incidence ( J:116152 )

• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)

• often show phenotypic change from expansive to invasive growth

• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis

increased metastatic potential ( J:116152 )

• in females presenting carcinomas ~1 cm in diameter, majority of tumors show extensive local invasion with ~50% demonstrating metastasis to draining and distant lymph nodes

• minority of animals show dissociated or loosely clustered lobulocarcinoma (ILC) cells in lungs, liver, gastrointestinal and urogenital tracts, and pancreas, or diffusely throughout peritoneal cavity

cardiovascular system

abnormal tumor vascularization ( J:116152 )

• mammary tumors show less vascularization, especially in periphery compared to double conditional null mice

integument

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth

• massive central necrosis is observed

increased skin tumor incidence ( J:116152 )

• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)

• often show phenotypic change from expansive to invasive growth

• tumors may invade subcutaneous fat or carnous muscle in irregular strands and nest with polymorphic cell with dyskeratosis

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (495 days) compared to double conditional knockouts (214 days)

• shift towards invasive from expansive carcinoma is observed with tumors classified as invasive lobulocarcinoma (ILC) developing multifocally in several mammary glands

• carcinosarcomas (having elements of carcinoma and sarcoma) develop, having spindle shaped cell morphology with large cells with pleomormphic nuclei; these display both expansive and invasive growth

• massive central necrosis is observed

Genotype
MGI:3695273

cn3

• Allelic Composition: Cdh1^tm1Jjon/Cdh1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT14-cre)8Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

neoplasm

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)

• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands

• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology

increased skin tumor incidence ( J:116152 )

• small numbers of skin carcinomas develop with latency of 330 days develop

• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis

increased pilomatricoma incidence ( J:116152 )

increased squamous cell carcinoma incidence ( J:116152 )

integument

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)

• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands

• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology

increased skin tumor incidence ( J:116152 )

• small numbers of skin carcinomas develop with latency of 330 days develop

• may be classified as pilomatriculomas or squamous cell carcinomas, without metastasis

increased pilomatricoma incidence ( J:116152 )

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:116152 )

• mice show longer tumor latency periods (330 days) compared to double conditional knockouts (214 days)

• most tumors are intermediate grade adenocarcinomas or high-grade solid carcinomas characterized by expansive growth pattern with large epithelial cells forming solid nest or irregular glands

• some tumors have a carcinosarcoma phenotype (elements of carcinoma and sarcoma) involving epithelial and mesenchymal elements with a metaphasic and biphasic histology

Genotype
MGI:3695274

cn4

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Tg(KRT14-cre)8Brn/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

normal phenotype

no abnormal phenotype detected ( J:116152 )

• virgin, pregnant, or parous females show no abnormalities in ductal or alveolar development

• dams are able to nurse litters normally

• mice show no predisposition to skin or mammary tumor development

Genotype
MGI:6296605

cn5

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Tg(Wap-cre)51Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

hypolactation ( J:171765 )

♀ • the produced quantity of milk is lower than in wild-type mice, even though females lactate and are able to nurse their litters

♀ • however, no morphological abnormalities in the mammary gland are seen in virgin, pregnant or parous females

integument

hypolactation ( J:171765 )

♀ • the produced quantity of milk is lower than in wild-type mice, even though females lactate and are able to nurse their litters

♀ • however, no morphological abnormalities in the mammary gland are seen in virgin, pregnant or parous females

neoplasm

neoplasm ( J:171765 )

♀N • none of the mice develop mammary carcinomas, even after induction of multiple pregnancies

Genotype
MGI:6296606

cn6

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Wap-cre)51Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

abnormal mammary gland growth during pregnancy ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development

♀ • as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition

abnormal mammary gland duct morphology ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show severe ectasia (dilated ducts)

♀ • however, mammary glands from virgin mice show no gross morphological abnormalities

abnormal mammary gland lobule morphology ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development, with effects becoming more pronounced as pregnancy progresses

increased mammary gland tumor incidence ( J:171765 )

♀ • mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands

♀ • most invasive lobular carcinomas are estrogen receptor negative

♀ • females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

lactation failure ( J:171765 )

♀ • mice produce healthy newborns, however all pups fostered by them die before weaning due to starvation

integument

abnormal mammary gland growth during pregnancy ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development

♀ • as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition

abnormal mammary gland duct morphology ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show severe ectasia (dilated ducts)

♀ • however, mammary glands from virgin mice show no gross morphological abnormalities

abnormal mammary gland lobule morphology ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development, with effects becoming more pronounced as pregnancy progresses

increased mammary gland tumor incidence ( J:171765 )

♀ • mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands

♀ • most invasive lobular carcinomas are estrogen receptor negative

♀ • females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

lactation failure ( J:171765 )

♀ • mice produce healthy newborns, however all pups fostered by them die before weaning due to starvation

neoplasm

increased mammary gland tumor incidence ( J:171765 )

♀ • mice develop mammary tumors with a reduced tumor-free survival age of 194 days, with most tumors arising between 150 and 250 days of age

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma and develop in high incidence multifocally in several mammary glands

♀ • most invasive lobular carcinomas are estrogen receptor negative

♀ • females also exhibit solid carcinoma/carcinosarcoma that predominantly show a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

increased metastatic potential ( J:171765 )

♀ • 74% of females that present mammary tumors of about 1 cm show extensive local invasion and metastases to draining and distant lymph nodes

♀ • invasive lobular carcinoma cells are seen in skin, lungs, liver, gastrointestinal tract, pancreas, and spleen or are diffusely disseminated throughout the peritoneal cavity

♀ • several mice develop bone metastases

reproductive system

abnormal mammary gland growth during pregnancy ( J:171765 )

♀ • mammary glands from females at day 14 of pregnancy show incomplete lobulo-alveolar development

♀ • as pregnancy progresses, the mammary gland fills with nonfunctional tissue resulting in complete disruption of the ductal structure at parturition

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
invasive lobular carcinoma		DOID:3457		J:171765

Genotype
MGI:6296608

cn7

• Allelic Composition: Cdh1^tm1Jjon/Cdh1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Wap-cre)51Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:171765 )

♀ • females develop mammary tumors with a median latency of around 290 days

♀ • mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

increased mammary adenocarcinoma incidence ( J:171765 )

♀ • some mice develop intermediate-grade adenocarcinoma

integument

increased mammary gland tumor incidence ( J:171765 )

♀ • females develop mammary tumors with a median latency of around 290 days

♀ • mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

increased mammary adenocarcinoma incidence ( J:171765 )

♀ • some mice develop intermediate-grade adenocarcinoma

neoplasm

increased mammary gland tumor incidence ( J:171765 )

♀ • females develop mammary tumors with a median latency of around 290 days

♀ • mammary tumors are either intermediate-grade adenocarcinoma or solid carcinoma/carcinosarcoma

♀ • virgin females develop mammary tumors with identical incidence and latency as uniparous females

♀ • tumor spectrum, invasiveness and metastatic dissemination are similar in virgin and parous females

increased mammary adenocarcinoma incidence ( J:171765 )

♀ • some mice develop intermediate-grade adenocarcinoma

Genotype
MGI:6296609

cn8

• Allelic Composition: Cdh1^tm1Jjon/Cdh1^tm1Jjon; Trp53^tm1Brn/Trp53⁺; Tg(Wap-cre)51Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:171765 )

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma

♀ • females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

hypolactation ( J:171765 )

♀ • pups show reduced survival rates due to inhibition or absence of lactation

integument

increased mammary gland tumor incidence ( J:171765 )

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma

♀ • females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

hypolactation ( J:171765 )

♀ • pups show reduced survival rates due to inhibition or absence of lactation

neoplasm

increased mammary gland tumor incidence ( J:171765 )

♀ • mice exhibit invasive mammary tumors which show phenotypic similarity to invasive lobular carcinoma

♀ • females also develop solid carcinoma/carcinosarcoma that predominantly exhibit a mixed epithelial and mesenchymal or spindle-shaped cell morphology and show both expansive and invasive growth patterns

increased metastatic potential ( J:171765 )

♀ • 70% of females that present mammary tumors of about 1 cm show extensive local invasion and metastases to draining and distant lymph nodes