Phenotypes associated with this allele

• Allele Symbol: Cdkn1b^tm1Ako
• Allele Name: targeted mutation 1, Andrew Koff
• Allele ID: MGI:1888808
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv	MGI:3839787
hm2	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * C57BL	MGI:3710690
hm3	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * C57BL/6	MGI:2175759
cn4	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838318
cn5	Cdkn1b^tm1Ako/Cdkn1b^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838319
cx6	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * 129S2/SvPas	MGI:4420547
cx7	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Men1^tm1.1Ctre/Men1^tm1.1Ctre	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6	MGI:3839789
cx8	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Men1^tm1.1Ctre/Men1^+	involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6	MGI:3839788
cx9	Cdk2^tm1Kald/Cdk2^tm1Kald Cdk4^tm1Kiyo/Cdk4^tm1Kiyo Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * C57BL/6	MGI:3639610
cx10	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Kit^W-v/Kit^W-v	involves: 129S1/Sv * C57BL/6J	MGI:5811260
cx11	Cdkn1b^tm1Ako/Cdkn1b^+ Kit^W-v/Kit^W-v	involves: 129S1/Sv * C57BL/6J	MGI:5811261
cx12	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	involves: 129/Sv * 129S1/Sv * C57BL/6 * DBA/2	MGI:3639679

Genotype
MGI:3839787

hm1

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv

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

adipose tissue

increased brown adipose tissue amount ( J:118516 )

• 25% compared to in wild-type mice

increased white fat cell number ( J:118516 )

• the number of adipocytes in the parametrial fat pad is increased 1.9-fold compared to in wild-type mice

• adipocyte hyperplasia is observed in small, medium, and large adipocytes

• the number of small adipocytes is increased 3-fold compared to in wild-type mice

increased inguinal fat pad weight ( J:118516 )

increased parametrial fat pad weight ( J:118516 )

• 80% at 130 days compared to in wild-type mice

respiratory system

increased lung adenocarcinoma incidence ( J:120835 )

• 8% of mice develop lung adenomas as solitary, uniform nodules with clear borders and homogeneous tumor cell type

neoplasm

increased ovary tumor incidence ( J:236161 )

• mice occasionally develop ovarian epithelial tumors

increased lung adenocarcinoma incidence ( J:120835 )

• 8% of mice develop lung adenomas as solitary, uniform nodules with clear borders and homogeneous tumor cell type

skeleton

abnormal tooth morphology ( J:102001 )

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type mice

growth/size/body

abnormal tooth morphology ( J:102001 )

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type mice

increased body weight ( J:118516 )

• at 60 to 120 days

increased kidney weight ( J:118516 )

• 37% compared to in wild-type mice

homeostasis/metabolism

decreased circulating testosterone level ( J:115443 )

increased circulating cholesterol level ( J:118516 )

abnormal response/metabolism to endogenous compounds ( J:115443 )

• testosterone treatment increases the seminal vesicle weight more than in similarly treated wild-type mice

nervous system

increased brain weight ( J:118516 )

renal/urinary system

increased kidney weight ( J:118516 )

• 37% compared to in wild-type mice

craniofacial

abnormal tooth morphology ( J:102001 )

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type mice

endocrine/exocrine glands

abnormal prostate gland dorsolateral lobe morphology ( J:115443 )

♂ • DNA content is increased 47% compared to in wild-type mice

increased ovary tumor incidence ( J:236161 )

• mice occasionally develop ovarian epithelial tumors

abnormal prostate gland physiology ( J:115443 )

♂ • ventral prostate and dorsolateral prostate epithelial proliferation is increased 2- and 3.8-fold, respectively, compared to in wild-type mice

♂ • luminal epithelial apoptosis is increased 8.7-fold compared to in wild-type mice

♂ • testosterone treatment does not alter increased luminal epithelial apoptosis rates

reproductive system

abnormal prostate gland dorsolateral lobe morphology ( J:115443 )

♂ • DNA content is increased 47% compared to in wild-type mice

increased ovary tumor incidence ( J:236161 )

• mice occasionally develop ovarian epithelial tumors

abnormal prostate gland physiology ( J:115443 )

♂ • ventral prostate and dorsolateral prostate epithelial proliferation is increased 2- and 3.8-fold, respectively, compared to in wild-type mice

♂ • luminal epithelial apoptosis is increased 8.7-fold compared to in wild-type mice

♂ • testosterone treatment does not alter increased luminal epithelial apoptosis rates

Genotype
MGI:3710690

hm2

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv * C57BL

cardiovascular system

decreased myocardial fiber size ( J:57380 )

• smaller myocyte size

increased myocardial fiber number ( J:57380 )

• 2-3-fold increase in the total number of cardiac myocytes

enlarged heart ( J:57380 )

• hearts are increased in size from 2 days of age onward

increased heart weight ( J:57380 )

• by 21 days of age, the wet weight of hearts are increased by more than 40%

heart hyperplasia ( J:57380 )

• prolonged duration of cardiac myocyte hyperplasia

abnormal fetal cardiomyocyte proliferation ( J:57380 )

• percentage of neonatal myocytes in S phase is increased, concomitant with a decrease in the percentage of G0/G1 cells, indicating prolonged proliferation of cardiac myocytes

muscle

decreased myocardial fiber size ( J:57380 )

• smaller myocyte size

increased myocardial fiber number ( J:57380 )

• 2-3-fold increase in the total number of cardiac myocytes

abnormal fetal cardiomyocyte proliferation ( J:57380 )

• percentage of neonatal myocytes in S phase is increased, concomitant with a decrease in the percentage of G0/G1 cells, indicating prolonged proliferation of cardiac myocytes

cellular

abnormal fetal cardiomyocyte proliferation ( J:57380 )

• percentage of neonatal myocytes in S phase is increased, concomitant with a decrease in the percentage of G0/G1 cells, indicating prolonged proliferation of cardiac myocytes

growth/size/body

enlarged heart ( J:57380 )

• hearts are increased in size from 2 days of age onward

increased heart weight ( J:57380 )

• by 21 days of age, the wet weight of hearts are increased by more than 40%

heart hyperplasia ( J:57380 )

• prolonged duration of cardiac myocyte hyperplasia

Genotype
MGI:2175759

hm3

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv * C57BL/6

growth/size/body

increased body weight ( J:33401 )

• weigh 20-40% more than littermate controls

increased spleen weight ( J:33401 )

• weight of spleen is increased relative to the increase in body size

endocrine/exocrine glands

abnormal pituitary intermediate lobe morphology ( J:50053 )

• at 30 weeks of age, a marked increase in vascularity is seen in the intermediate lobe, manifested as lakes of distended capillaries filled with red blood cells

pituitary intermediate lobe hyperplasia ( J:33401 , J:50053 )

increased pituitary gland tumor incidence ( J:50053 )

• older mice (8 and 11 months of age) develop pituitary tumors, however none die of the tumors

increased thymus weight ( J:33401 )

• weight of thymus is increased relative to the increase in body size

increased thymocyte number ( J:33401 )

• detect an increase in the number of splenic T cells and an increase in the number of proliferating thymocytes in the thymus, in both the cortical and medullary regions

abnormal corpus luteum morphology ( J:33401 )

♀ • ovaries show defective formation of the corpus luteum

immune system

increased thymus weight ( J:33401 )

• weight of thymus is increased relative to the increase in body size

increased thymocyte number ( J:33401 )

• detect an increase in the number of splenic T cells and an increase in the number of proliferating thymocytes in the thymus, in both the cortical and medullary regions

increased spleen weight ( J:33401 )

• weight of spleen is increased relative to the increase in body size

reproductive system

abnormal corpus luteum morphology ( J:33401 )

♀ • ovaries show defective formation of the corpus luteum

prolonged estrus ( J:33401 )

♀ • females typically show a prolongation prior to oestrous and a delay in exiting oestrous

prolonged estrous cycle ( J:33401 )

♀ • females exhibit prolonged oestrous cycles

female infertility ( J:33401 )

♀ • although ovulation and fertilization occur, females do not maintain pregnancies

hematopoietic system

increased thymus weight ( J:33401 )

• weight of thymus is increased relative to the increase in body size

increased thymocyte number ( J:33401 )

• detect an increase in the number of splenic T cells and an increase in the number of proliferating thymocytes in the thymus, in both the cortical and medullary regions

increased spleen weight ( J:33401 )

• weight of spleen is increased relative to the increase in body size

nervous system

abnormal pituitary intermediate lobe morphology ( J:50053 )

• at 30 weeks of age, a marked increase in vascularity is seen in the intermediate lobe, manifested as lakes of distended capillaries filled with red blood cells

pituitary intermediate lobe hyperplasia ( J:33401 , J:50053 )

increased pituitary gland tumor incidence ( J:50053 )

• older mice (8 and 11 months of age) develop pituitary tumors, however none die of the tumors

neoplasm

increased pituitary gland tumor incidence ( J:50053 )

• older mice (8 and 11 months of age) develop pituitary tumors, however none die of the tumors

Genotype
MGI:4838318

cn4

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako; Pten^tm2.1Ppp/Pten^tm2.1Ppp; Tg(TPO-cre)1Shk/0
• Genetic Background: 129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp

mortality/aging

premature death ( J:165293 )

• mean survival is 21 weeks and all mutants die by 6 months of age

endocrine/exocrine glands

thyroid gland hyperplasia ( J:165293 )

respiratory system

respiratory distress ( J:165293 )

• hyperplastic thyroids cause dyspnea and prevent feeding

Genotype
MGI:4838319

cn5

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b⁺; Pten^tm2.1Ppp/Pten^tm2.1Ppp; Tg(TPO-cre)1Shk/0
• Genetic Background: 129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp

mortality/aging

premature death ( J:165293 )

• mean survival is 58 weeks of age

neoplasm

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

Genotype
MGI:4420547

cx6

• Allelic Composition: Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj; Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas

digestive/alimentary system

abnormal junctional epithelium morphology ( J:102001 )

• the total area of the periodontal junctional epithelium and connective tissue islands is larger than in wild-type or single heterozygous mice

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type and heterozygous mice

• the number of proliferating cells in the junctional epithelium is increased compared to in wild-type or single heterozygous mice

adipose tissue

increased brown adipose tissue amount ( J:118516 )

• 142% compared to in wild-type mice

increased total body fat amount ( J:118516 )

increased white fat cell number ( J:118516 )

• the number of adipocytes in the parametrial fat pad is increased 6.1-fold compared to in wild-type mice

• adipocyte hyperplasia is observed in small, medium, and large adipocytes

• the number of small adipocytes is increased 9.5-fold compared to in wild-type mice

increased inguinal fat pad weight ( J:118516 )

increased parametrial fat pad weight ( J:118516 )

• 500% at 130 days compared to in wild-type mice

behavior/neurological

increased food intake ( J:118516 )

• from 30 to 120 days, mice consume 40% more food than wild-type mice

• however, feed consumption per gram of lean body weight is normal

growth/size/body

abnormal junctional epithelium morphology ( J:102001 )

• the total area of the periodontal junctional epithelium and connective tissue islands is larger than in wild-type or single heterozygous mice

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type and heterozygous mice

• the number of proliferating cells in the junctional epithelium is increased compared to in wild-type or single heterozygous mice

increased lean body mass ( J:118516 )

• 24% at 120 days compared to in wild-type mice

increased body weight ( J:115443 , J:118516 )

• at 60 to 120 days compared with wild-type and single homozygous mice (J:118516)

increased kidney weight ( J:118516 )

• 105% compared to in wild-type mice

homeostasis/metabolism

decreased circulating testosterone level ( J:115443 )

increased circulating cholesterol level ( J:118516 )

impaired glucose tolerance ( J:118516 )

insulin resistance ( J:118516 )

liver/biliary system

hepatic steatosis ( J:118516 )

nervous system

increased brain weight ( J:118516 )

renal/urinary system

increased kidney weight ( J:118516 )

• 105% compared to in wild-type mice

craniofacial

abnormal junctional epithelium morphology ( J:102001 )

• the total area of the periodontal junctional epithelium and connective tissue islands is larger than in wild-type or single heterozygous mice

• the total area of connective tissue islands in the junctional epithelium is larger than in wild-type and heterozygous mice

• the number of proliferating cells in the junctional epithelium is increased compared to in wild-type or single heterozygous mice

endocrine/exocrine glands

decreased prostate gland anterior lobe weight ( J:115443 )

♂ • prostate gland anterior lobe weight is decreased 68% compared to in wild-type mice

decreased prostate gland dorsolateral lobe weight ( J:115443 )

♂ • prostate gland dorsolateral lobe weight is decreased 68% compared to in wild-type mice

decreased prostate gland ventral lobe weight ( J:115443 )

♂ • prostate gland ventral lobe weight is decreased 60% compared to in wild-type mice

decreased seminal vesicle weight ( J:115443 )

♂ • 75% compared to in wild-type mice

reproductive system

decreased prostate gland anterior lobe weight ( J:115443 )

♂ • prostate gland anterior lobe weight is decreased 68% compared to in wild-type mice

decreased prostate gland dorsolateral lobe weight ( J:115443 )

♂ • prostate gland dorsolateral lobe weight is decreased 68% compared to in wild-type mice

decreased prostate gland ventral lobe weight ( J:115443 )

♂ • prostate gland ventral lobe weight is decreased 60% compared to in wild-type mice

decreased seminal vesicle weight ( J:115443 )

♂ • 75% compared to in wild-type mice

Genotype
MGI:3839789

cx7

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako; Men1^tm1.1Ctre/Men1^tm1.1Ctre
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6

mortality/aging

embryonic lethality, complete penetrance ( J:120835 )

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

Genotype
MGI:3839788

cx8

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako; Men1^tm1.1Ctre/Men1⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6

neoplasm

increased tumor incidence ( J:120835 )

• mice develop tumors of the pituitary, thyroid, parathyroid, pancreas, adrenal and testis

increased adrenal gland tumor incidence ( J:120835 )

increased pituitary 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 )

♂

increased lung adenoma incidence ( J:120835 )

• in 6 % of mice

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:120835 )

increased pituitary 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 )

♂

reproductive system

increased testis tumor incidence ( J:120835 )

♂

nervous system

increased pituitary gland tumor incidence ( J:120835 )

respiratory system

increased lung adenoma incidence ( J:120835 )

• in 6 % of mice

Genotype
MGI:3639610

cx9

• Allelic Composition: Cdk2^tm1Kald/Cdk2^tm1Kald; Cdk4^tm1Kiyo/Cdk4^tm1Kiyo; Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:108720 )

• embryos appear normal at E13.5 and die around E15.5

cellular

decreased cell proliferation ( J:108720 )

• MEFs show decreased proliferation rate

Genotype
MGI:5811260

cx10

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b^tm1Ako; Kit^W-v/Kit^W-v
• Genetic Background: involves: 129S1/Sv * C57BL/6J

neoplasm

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% or less of granulosa cells

endocrine/exocrine glands

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% or less of granulosa cells

abnormal ovary physiology ( J:236161 )

• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants

reproductive system

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% or less of granulosa cells

abnormal ovary physiology ( J:236161 )

• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:236161

Genotype
MGI:5811261

cx11

• Allelic Composition: Cdkn1b^tm1Ako/Cdkn1b⁺; Kit^W-v/Kit^W-v
• Genetic Background: involves: 129S1/Sv * C57BL/6J

mortality/aging

premature death ( J:236161 )

• sudden death is frequently seen

neoplasm

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

• in aged mice, large ovarian tumors develop, infiltrate, and occupy the entire para- and meso-ovarian regions

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• ovaries have a tumor phenotype that is more prominent than the tubular adenomas of the double homozygous ovaries

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% of less of granulosa cells

endocrine/exocrine glands

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

• in aged mice, large ovarian tumors develop, infiltrate, and occupy the entire para- and meso-ovarian regions

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• ovaries have a tumor phenotype that is more prominent than the tubular adenomas of the double homozygous ovaries

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% of less of granulosa cells

abnormal ovary physiology ( J:236161 )

• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants

reproductive system

increased ovary tumor incidence ( J:236161 )

• mice exhibit enlarged ovarian tumors compared to single Kit homozygous mutants

• in aged mice, large ovarian tumors develop, infiltrate, and occupy the entire para- and meso-ovarian regions

increased ovary adenoma incidence ( J:236161 )

• ovarian tubular adenomas are bilateral

• ovaries have a tumor phenotype that is more prominent than the tubular adenomas of the double homozygous ovaries

• papillary ovarian tubular adenomas from 8 month old mice have CK8+ epithelial cells infiltrating the entire ovary, the bursa and surrounding areas and resemble ovarian cancer or severe ovarian surface papillomatosis

• however, the epithelial lesions of ovarian tumors are benign

• tumor mass is largely epithelial and contains a minor 10% of less of granulosa cells

abnormal ovary physiology ( J:236161 )

• ovarian epithelial cells show enhanced cell proliferation in culture compared to single homozygous Kit mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:236161

Genotype
MGI:3639679

cx12

• 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 )