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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Cdkn2ctm1Yxi
targeted mutation 1, Yue Xiong
MGI:1933762
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi B6.129-Cdkn2ctm1Yxi MGI:3839784
hm2
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi C.129-Cdkn2ctm1Yxi MGI:5517369
hm3
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi involves: 129/Sv * C57BL/6 * DBA/2 MGI:2175774
cx4
Brca1tm1Bhk/Brca1+
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
C.129-Cdkn2ctm1Yxi Brca1tm1Bhk MGI:5517370
cx5
Brca1tm1Bhk/Brca1tm1Bhk
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
C.129-Cdkn2ctm1Yxi Brca1tm1Bhk MGI:5517367
cx6
Cdkn1btm1Ako/Cdkn1btm1Ako
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
involves: 129/Sv * 129S1/Sv * C57BL/6 * DBA/2 MGI:3639679
cx7
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Men1tm1.1Ctre/Men1+
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 MGI:3839785
cx8
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Men1tm1.1Ctre/Men1tm1.1Ctre
involves: 129/Sv * 129S6/SvEvTac * C57BL/6 MGI:3839786


Genotype
MGI:3839784
hm1
Allelic
Composition
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
B6.129-Cdkn2ctm1Yxi
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• lung tumors develop in 20% of mice and are solitary, uniform nodules with clear borders and homogeneous tumor cell type
• bronchioalveolar stem cells are expanded in lung tumors

respiratory system
• lung tumors develop in 20% of mice and are solitary, uniform nodules with clear borders and homogeneous tumor cell type
• bronchioalveolar stem cells are expanded in lung tumors
• bronchioalveolar stem cells are expanded compared to in wild-type mice




Genotype
MGI:5517369
hm2
Allelic
Composition
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
C.129-Cdkn2ctm1Yxi
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mammary glands of virgin females are enriched with luminal stem/progenitors at 6 weeks and 9 months of age compared to wild-type females
• 25% of mutants develop breast cancer before 1 year of age and 83% by 22 months of age
• 79% of tumors are positive for ERalpha and tumors are predominately luminal-like
• only 1 of 19 (5.3%) mammary tumors metastasize to the lung after 1 year of age

integument
• mammary glands of virgin females are enriched with luminal stem/progenitors at 6 weeks and 9 months of age compared to wild-type females
• 25% of mutants develop breast cancer before 1 year of age and 83% by 22 months of age
• 79% of tumors are positive for ERalpha and tumors are predominately luminal-like
• only 1 of 19 (5.3%) mammary tumors metastasize to the lung after 1 year of age

neoplasm
• 25% of mutants develop breast cancer before 1 year of age and 83% by 22 months of age
• 79% of tumors are positive for ERalpha and tumors are predominately luminal-like
• only 1 of 19 (5.3%) mammary tumors metastasize to the lung after 1 year of age




Genotype
MGI:2175774
hm3
Allelic
Composition
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
involves: 129/Sv * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 10-month or older mice that develop a large pituitary adenoma appear thin
• become larger within 2-3 weeks of age
• body weight increases by 20%, 40%, and 30% at 1, 2, and 3 months of age, respectively
• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively
• exhibit increased cellularity in the spleen at 2 months of age

neoplasm
• develop intermediate lobe adenoma at 9 to 13 months of age

endocrine/exocrine glands
• disproportionate enlargement
• disproportionate and progressive enlargement
• age-dependent progression of pituitary gland hyperplasia, from mild intermediate lobe hyperplasia to moderate and severe hyperplasia, compression of adjacent lobes, and finally the development of intermediate lobe adenoma
• disproportionately enlarged; thymus weight is twice the body weight increase at 1 month, becomes proportionate to body weight increase at 2 months, and is disproportionately small at 3 months
• show a 40% increase in thymic cellularity
• although larger than wild-type testes, the testes of 1, 2, and 3 month old males are disproportionately small with respect to the body size
• develop intermediate lobe adenoma at 9 to 13 months of age

immune system
• disproportionately enlarged; thymus weight is twice the body weight increase at 1 month, becomes proportionate to body weight increase at 2 months, and is disproportionately small at 3 months
• show a 40% increase in thymic cellularity
• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively
• exhibit increased cellularity in the spleen at 2 months of age
• increased expansion of activated B cells
• display expansion of T lymphocytes
• T lymphocytes are hyper-responsive to mitogenic stimulation

behavior/neurological
• 10-month or older mice that develop a large pituitary adenoma are ataxic

homeostasis/metabolism
• 10-month or older mice that develop a large pituitary adenoma are dehydrated

reproductive system
• although larger than wild-type testes, the testes of 1, 2, and 3 month old males are disproportionately small with respect to the body size

hematopoietic system
• disproportionately enlarged; thymus weight is twice the body weight increase at 1 month, becomes proportionate to body weight increase at 2 months, and is disproportionately small at 3 months
• show a 40% increase in thymic cellularity
• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively
• exhibit increased cellularity in the spleen at 2 months of age
• show increased cellularity in the bone marrow at 2 months of age
• increased expansion of activated B cells
• display expansion of T lymphocytes
• T lymphocytes are hyper-responsive to mitogenic stimulation

nervous system
• disproportionate and progressive enlargement
• age-dependent progression of pituitary gland hyperplasia, from mild intermediate lobe hyperplasia to moderate and severe hyperplasia, compression of adjacent lobes, and finally the development of intermediate lobe adenoma
• develop intermediate lobe adenoma at 9 to 13 months of age




Genotype
MGI:5517370
cx4
Allelic
Composition
Brca1tm1Bhk/Brca1+
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
C.129-Cdkn2ctm1Yxi Brca1tm1Bhk
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Brca1tm1Bhk mutation (0 available); any Brca1 mutation (87 available)
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mammary glands of virgin females show a decrease in the expansion of luminal progenitors seen in single Cdkn2c homozygotes to normal levels but show an increase in the expansion of basal/myoepithelial cells
• 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age
• mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis
• mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype
• poorly differentiated carcinoma with squamous metaplasia

integument
• mammary glands of virgin females show a decrease in the expansion of luminal progenitors seen in single Cdkn2c homozygotes to normal levels but show an increase in the expansion of basal/myoepithelial cells
• 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age
• mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis
• mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype
• poorly differentiated carcinoma with squamous metaplasia

neoplasm
• 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age
• mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis
• mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype
• poorly differentiated carcinoma with squamous metaplasia
• 4 of 13 (31%) mammary tumors metastasize to the lung and blood vessels after 1 year of age

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
breast cancer DOID:1612 OMIM:114480
J:198018




Genotype
MGI:5517367
cx5
Allelic
Composition
Brca1tm1Bhk/Brca1tm1Bhk
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
C.129-Cdkn2ctm1Yxi Brca1tm1Bhk
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Brca1tm1Bhk mutation (0 available); any Brca1 mutation (87 available)
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• no viable embryos are identified beyond E14.5




Genotype
MGI:3639679
cx6
Allelic
Composition
Cdkn1btm1Ako/Cdkn1btm1Ako
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Genetic
Background
involves: 129/Sv * 129S1/Sv * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1btm1Ako mutation (0 available); any Cdkn1b mutation (11 available)
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• all die by 3.5 months of pituitary tumors

growth/size/body
• appear thin by 3 months of age

behavior/neurological
• appear ataxic by 3 months of age

homeostasis/metabolism
• appear dehydrated by 3 months of age

neoplasm
• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice
• one mutant developed a pituitary carcinoma

cardiovascular system

endocrine/exocrine glands
• pituitary glands are larger than in single homozygous mutants
• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice

hematopoietic system

reproductive system

nervous system
• pituitary glands are larger than in single homozygous mutants
• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice

immune system




Genotype
MGI:3839785
cx7
Allelic
Composition
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Men1tm1.1Ctre/Men1+
Genetic
Background
involves: 129/Sv * 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
Men1tm1.1Ctre mutation (2 available); any Men1 mutation (29 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• some mice exhibit Leydig cell adenocarcinomas
• some mice exhibit Leydig cell adenocarcinomas

respiratory system
• most lung tumors are primary
• bronchioalveolar stem cells are expanded in lung tumors compared to in Cdkn2ctm1Yxi homozygotes or Men1tm1.1Ctre heterozygotes
• in 33% of mice before 1 year of age
• after 1 year of age, lung adenocarcinomas develop in 63% of mice including 3 carcinomas with neuroendocrine characteristics
• mice develop multiple lung carcinomas that are more aggressive and invasive than in single mutant mice
• neuroendocrine carcinomas are more proliferative and apoptotic than in single mutant mice

reproductive system
• some mice exhibit Leydig cell adenocarcinomas
• some mice exhibit Leydig cell adenocarcinomas

neoplasm
• some mice exhibit Leydig cell adenocarcinomas
• some mice exhibit Leydig cell adenocarcinomas
• some mice exhibit Leydig cell adenocarcinomas
• most lung tumors are primary
• bronchioalveolar stem cells are expanded in lung tumors compared to in Cdkn2ctm1Yxi homozygotes or Men1tm1.1Ctre heterozygotes
• in 33% of mice before 1 year of age
• after 1 year of age, lung adenocarcinomas develop in 63% of mice including 3 carcinomas with neuroendocrine characteristics
• mice develop multiple lung carcinomas that are more aggressive and invasive than in single mutant mice
• neuroendocrine carcinomas are more proliferative and apoptotic than in single mutant mice
• tumors develop quicker than in Men1tm1.1Ctre heterozygotes




Genotype
MGI:3839786
cx8
Allelic
Composition
Cdkn2ctm1Yxi/Cdkn2ctm1Yxi
Men1tm1.1Ctre/Men1tm1.1Ctre
Genetic
Background
involves: 129/Sv * 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2ctm1Yxi mutation (1 available); any Cdkn2c mutation (10 available)
Men1tm1.1Ctre mutation (2 available); any Men1 mutation (29 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• no viable double homozygous embryos were present beyond E15.5





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
03/30/2021
MGI 6.16
The Jackson Laboratory