Phenotypes associated with this allele

• Allele Symbol: Cdkn2c^tm1Yxi
• Allele Name: targeted mutation 1, Yue Xiong
• Allele ID: MGI:1933762
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	B6.129-Cdkn2c^tm1Yxi	MGI:3839784
hm2	Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	C.129-Cdkn2c^tm1Yxi	MGI:5517369
hm3	Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	involves: 129/Sv * C57BL/6 * DBA/2	MGI:2175774
cx4	Brca1^tm1Bhk/Brca1^+ Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk	MGI:5517370
cx5	Brca1^tm1Bhk/Brca1^tm1Bhk Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk	MGI:5517367
cx6	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	involves: 129/Sv * 129S1/Sv * C57BL/6 * DBA/2	MGI:3639679
cx7	Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi Men1^tm1.1Ctre/Men1^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6	MGI:3839785
cx8	Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi Men1^tm1.1Ctre/Men1^tm1.1Ctre	involves: 129/Sv * 129S6/SvEvTac * C57BL/6	MGI:3839786

Genotype
MGI:3839784

hm1

• Allelic Composition: Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: B6.129-Cdkn2c^tm1Yxi

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

neoplasm

increased lung tumor incidence ( J:120835 )

• 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

increased lung adenoma incidence ( J:120835 )

• in 1 mouse

increased lung adenocarcinoma incidence ( J:120835 )

• in 1 mouse

respiratory system

increased lung tumor incidence ( J:120835 )

• 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

increased lung adenoma incidence ( J:120835 )

• in 1 mouse

increased lung adenocarcinoma incidence ( J:120835 )

• in 1 mouse

increased bronchioalveolar stem cell number ( J:120835 )

• bronchioalveolar stem cells are expanded compared to in wild-type mice

Genotype
MGI:5517369

hm2

• Allelic Composition: Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: C.129-Cdkn2c^tm1Yxi

endocrine/exocrine glands

abnormal mammary gland morphology ( J:198018 )

♀ • mammary glands of virgin females are enriched with luminal stem/progenitors at 6 weeks and 9 months of age compared to wild-type females

increased mammary gland tumor incidence ( J:198018 )

♀ • 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

abnormal mammary gland morphology ( J:198018 )

♀ • mammary glands of virgin females are enriched with luminal stem/progenitors at 6 weeks and 9 months of age compared to wild-type females

increased mammary gland tumor incidence ( J:198018 )

♀ • 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

increased mammary gland tumor incidence ( J:198018 )

♀ • 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: Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

growth/size/body

weight loss ( J:50053 )

• 10-month or older mice that develop a large pituitary adenoma appear thin

increased body size ( J:50053 )

• become larger within 2-3 weeks of age

increased body weight ( J:50053 )

• body weight increases by 20%, 40%, and 30% at 1, 2, and 3 months of age, respectively

enlarged spleen ( J:50053 )

• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively

spleen hyperplasia ( J:50053 )

• exhibit increased cellularity in the spleen at 2 months of age

neoplasm

increased pituitary adenoma incidence ( J:50053 )

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

endocrine/exocrine glands

enlarged adrenal glands ( J:50053 )

• disproportionate enlargement

enlarged pituitary gland ( J:50053 )

• disproportionate and progressive enlargement

pituitary gland hyperplasia ( J:50053 )

• 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

abnormal pituitary intermediate lobe morphology ( J:50053 )

increased pituitary adenoma incidence ( J:50053 )

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

abnormal thymus size ( J:50053 )

• 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

thymus hyperplasia ( J:50053 )

• show a 40% increase in thymic cellularity

small testis ( J:50053 )

♂ • 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

immune system

abnormal thymus size ( J:50053 )

• 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

thymus hyperplasia ( J:50053 )

• show a 40% increase in thymic cellularity

enlarged spleen ( J:50053 )

• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively

spleen hyperplasia ( J:50053 )

• exhibit increased cellularity in the spleen at 2 months of age

increased B cell number ( J:50053 )

• increased expansion of activated B cells

increased T cell number ( J:50053 )

• display expansion of T lymphocytes

abnormal T cell physiology ( J:50053 )

• T lymphocytes are hyper-responsive to mitogenic stimulation

behavior/neurological

ataxia ( J:50053 )

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

homeostasis/metabolism

dehydration ( J:50053 )

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

reproductive system

small testis ( J:50053 )

♂ • 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

abnormal thymus size ( J:50053 )

• 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

thymus hyperplasia ( J:50053 )

• show a 40% increase in thymic cellularity

enlarged spleen ( J:50053 )

• disproportionately enlarged by 40%, 110%, and 90% at 1, 2, and 3 months of age, respectively

spleen hyperplasia ( J:50053 )

• exhibit increased cellularity in the spleen at 2 months of age

increased bone marrow cell number ( J:50053 )

• show increased cellularity in the bone marrow at 2 months of age

increased B cell number ( J:50053 )

• increased expansion of activated B cells

increased T cell number ( J:50053 )

• display expansion of T lymphocytes

abnormal T cell physiology ( J:50053 )

• T lymphocytes are hyper-responsive to mitogenic stimulation

nervous system

enlarged pituitary gland ( J:50053 )

• disproportionate and progressive enlargement

pituitary gland hyperplasia ( J:50053 )

• 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

abnormal pituitary intermediate lobe morphology ( J:50053 )

increased pituitary adenoma incidence ( J:50053 )

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

Genotype
MGI:5517370

cx4

• Allelic Composition: Brca1^tm1Bhk/Brca1⁺; Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk

endocrine/exocrine glands

abnormal mammary gland morphology ( J:198018 )

♀ • 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

increased mammary gland tumor incidence ( J:198018 )

♀ • 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

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

integument

abnormal mammary gland morphology ( J:198018 )

♀ • 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

increased mammary gland tumor incidence ( J:198018 )

♀ • 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

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

neoplasm

increased mammary gland tumor incidence ( J:198018 )

♀ • 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

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

increased metastatic potential ( J:198018 )

• 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: Brca1^tm1Bhk/Brca1^tm1Bhk; Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:198018 )

• no viable embryos are identified beyond E14.5

Genotype
MGI:3639679

cx6

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako; Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: involves: 129/Sv * 129S1/Sv * C57BL/6 * DBA/2

mortality/aging

decreased tumor-free survival time ( J:50053 )

• all die by 3.5 months of pituitary tumors

growth/size/body

enlarged heart ( J:50053 )

weight loss ( J:50053 )

• appear thin by 3 months of age

enlarged spleen ( J:50053 )

behavior/neurological

ataxia ( J:50053 )

• appear ataxic by 3 months of age

homeostasis/metabolism

dehydration ( J:50053 )

• appear dehydrated by 3 months of age

neoplasm

increased pituitary adenoma incidence ( J:50053 )

• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice

increased carcinoma incidence ( J:50053 )

• one mutant developed a pituitary carcinoma

cardiovascular system

enlarged heart ( J:50053 )

endocrine/exocrine glands

enlarged adrenal glands ( J:50053 )

enlarged pituitary gland ( J:50053 )

• pituitary glands are larger than in single homozygous mutants

pituitary intermediate lobe hyperplasia ( J:50053 )

• lobe is hyperplastic

increased pituitary adenoma incidence ( J:50053 )

• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice

enlarged thymus ( J:50053 )

enlarged testis ( J:50053 )

♂

hematopoietic system

enlarged thymus ( J:50053 )

enlarged spleen ( J:50053 )

reproductive system

enlarged testis ( J:50053 )

♂

nervous system

enlarged pituitary gland ( J:50053 )

• pituitary glands are larger than in single homozygous mutants

pituitary intermediate lobe hyperplasia ( J:50053 )

• lobe is hyperplastic

increased pituitary adenoma incidence ( J:50053 )

• develop pituitary tumors (by 3 months of age) at an accelerated rate compared to the single homozygous mice

immune system

enlarged thymus ( J:50053 )

enlarged spleen ( J:50053 )

Genotype
MGI:3839785

cx7

• Allelic Composition: Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi; Men1^tm1.1Ctre/Men1⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6

neoplasm

increased adrenal gland tumor incidence ( J:120835 )

increased parathyroid gland tumor incidence ( J:120835 )

increased thyroid tumor incidence ( J:120835 )

increased pancreas tumor incidence ( J:120835 )

increased testis tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

increased Leydig cell tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

increased adenocarcinoma incidence ( J:120835 )

• some mice exhibit Leydig cell adenocarcinomas

increased lung tumor incidence ( J:120835 )

• most lung tumors are primary

• bronchioalveolar stem cells are expanded in lung tumors compared to in Cdkn2c^tm1Yxi homozygotes or Men1^tm1.1Ctre heterozygotes

increased lung adenoma incidence ( J:120835 )

• in 33% of mice before 1 year of age

increased lung adenocarcinoma incidence ( J:120835 )

• 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

decreased tumor latency ( J:120835 )

• tumors develop quicker than in Men1^tm1.1Ctre heterozygotes

reproductive system

increased testis tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

increased Leydig cell tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

respiratory system

increased lung tumor incidence ( J:120835 )

• most lung tumors are primary

• bronchioalveolar stem cells are expanded in lung tumors compared to in Cdkn2c^tm1Yxi homozygotes or Men1^tm1.1Ctre heterozygotes

increased lung adenoma incidence ( J:120835 )

• in 33% of mice before 1 year of age

increased lung adenocarcinoma incidence ( J:120835 )

• 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

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:120835 )

increased parathyroid gland tumor incidence ( J:120835 )

increased thyroid tumor incidence ( J:120835 )

increased pancreas tumor incidence ( J:120835 )

increased testis tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

increased Leydig cell tumor incidence ( J:120835 )

♂ • some mice exhibit Leydig cell adenocarcinomas

Genotype
MGI:3839786

cx8

• Allelic Composition: Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi; Men1^tm1.1Ctre/Men1^tm1.1Ctre
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6

mortality/aging

embryonic lethality, complete penetrance ( J:120835 )

• no viable double homozygous embryos were present beyond E15.5