All Phenotypes Cdkn1a<tm1Tyj> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Cdkn1a^tm1Tyj
targeted mutation 1, Tyler Jacks
MGI:1933751

Summary

27 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	B6;129S2-Cdkn1a^tm1Tyj/J	MGI:3699911
hm2	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S1/SvImJ * 129S2/SvPas * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5749465
hm3	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J	MGI:4420543
hm4	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S2/SvPas	MGI:2175758
hm5	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3706343
hm6	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129/Sv * 129S2/SvPas * C57BL/6	MGI:4420541
ht7	Cdkn1a^tm1Tyj/Cdkn1a⁺	involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J	MGI:4420544
cn8	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543696
cn9	Brca1^tm2Mak/Brca1^tm2Mak Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(Lck-cre)548Jxm/?	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3834732
cn10	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Pten^tm1Hwu/Pten^tm1Hwu Tg(Fabp1-cre)1Jig/0	involves: 129S2/SvPas * 129S4/SvJae * FVB/N	MGI:4844100
cn11	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Itgb1^tm1Mll/Itgb1^tm1Mll Tg(Wap-cre)1Gsc/0	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * FVB/N	MGI:3706341
cx12	Apoe^tm1Unc/Apoe^tm1Unc Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	B6.129-Apoe^tm1Unc Cdkn1a^tm1Tyj	MGI:4420802
cx13	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Gadd45a^tm1Ajf/Gadd45a^tm1Ajf	either: (involves: 129P2/OlaHsd) or (involves: 129X1/SvJ)	MGI:4420763
cx14	Brca1^tm1Mak/Brca1^tm1Mak Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:4420437
cx15	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2d^tm1Maro/Cdkn2d^tm1Maro	involves: 129P2/OlaHsd * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CD-1	MGI:4420894
cx16	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * 129S2/SvPas	MGI:4420547
cx17	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Gata1^tm1.1Yen/Gata1^tm1.1Yen	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5522831
cx18	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Zfpm2^tm1.1Esv/Zfpm2^tm1.1Esv	involves: 129S1/SvImJ * 129S2/SvPas * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5749463
cx19	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420467
cx20	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0	involves: 129S2/SvPas	MGI:4420466
cx21	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Foxk1^tm1Djg/Foxk1^tm1Djg	involves: 129S2/SvPas * 129S4/SvJae	MGI:3655091
cx22	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf	involves: 129S2/SvPas * 129S4/SvJaeSor	MGI:4420782
cx23	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Palb2^tm1.2Dli/Palb2^tm1.2Dli	involves: 129S2/SvPas * 129S4/SvJaeSor * BALB/cJ * C57BL/6	MGI:5495976
cx24	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Fah^tm1Mgo/Fah^tm1Mgo	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:4420927
cx25	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Mir34a^tm1.1Lhe/Mir34a^tm1.1Lhe	involves: 129S2/SvPas * C57BL/6 * C57BL/6J	MGI:5308802
cx26	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(MMTV-vHaras)SH1Led/0	involves: 129S2/SvPas * C57BL/6J * CD-1 * FVB/N	MGI:3706374
cx27	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp	involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:4420540

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	B6;129S2-Cdkn1a^tm1Tyj/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

immune system

impaired macrophage chemotaxis ( J:108569 )

• in a serum transfer model of inflammatory arthritis, fewer macrophages are recruited to the site of inflammation compared to in similarly treated wild-type mice

• following intraperitoneal thioglycollate injection, fewer macrophages are recruited into the peritoneum compared to in similarly treated wild-type mice

• however, in vitro migration of bone marrow derived macrophages is normal in response to several chemoattractants

decreased monocyte cell number ( J:108569 )

• circulating inflammatory monocytes are reduced compared to in wild-type mice

decreased susceptibility to induced arthritis ( J:108569 )

• in a serum transfer model of inflammatory arthritis, mice exhibit no inflammation, lower histological scores, and reduced macrophage infiltration compared with similarly treated wild-type mice

• however, adoptive transfer of wild-type bone marrow restores susceptibility to induced arthritis

hematopoietic system

impaired macrophage chemotaxis ( J:108569 )

• in a serum transfer model of inflammatory arthritis, fewer macrophages are recruited to the site of inflammation compared to in similarly treated wild-type mice

• following intraperitoneal thioglycollate injection, fewer macrophages are recruited into the peritoneum compared to in similarly treated wild-type mice

• however, in vitro migration of bone marrow derived macrophages is normal in response to several chemoattractants

abnormal bone marrow cell morphology/development ( J:108569 )

• fewer monocyte precursors are found within the bone marrow compared to in wild-type mice

decreased monocyte cell number ( J:108569 )

• circulating inflammatory monocytes are reduced compared to in wild-type mice

skeleton

decreased susceptibility to induced arthritis ( J:108569 )

• in a serum transfer model of inflammatory arthritis, mice exhibit no inflammation, lower histological scores, and reduced macrophage infiltration compared with similarly treated wild-type mice

• however, adoptive transfer of wild-type bone marrow restores susceptibility to induced arthritis

cellular

impaired macrophage chemotaxis ( J:108569 )

• in a serum transfer model of inflammatory arthritis, fewer macrophages are recruited to the site of inflammation compared to in similarly treated wild-type mice

• following intraperitoneal thioglycollate injection, fewer macrophages are recruited into the peritoneum compared to in similarly treated wild-type mice

• however, in vitro migration of bone marrow derived macrophages is normal in response to several chemoattractants

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:98518 )

• contrary to expectation, homozygotes display a normal inner ear morphology relative to wild-type mice

• at E16.5, E18.5, P2 and 2 months of age, no significant differences in the cytoarchitecture of vestibular and auditory sensory epithelia or aberrant mitoses in developing hair cells are observed

cardiovascular system

cardiovascular system phenotype ( J:216295 )

N	• at birth, homozygotes display normal heart histology, with no signs of overproliferation or thickening of the ventricular wall

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129S1/SvImJ * 129S2/SvPas * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

cardiovascular system

cardiovascular system phenotype ( J:216295 )

N	• at P0, homozygotes display normal left ventricular function relative to wild-type controls, as determined by chamber dimensions and fractional shortening

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

neoplasm

increased metastatic potential ( J:83967 )

• irradiated mice develop 2.7-fold more metastatic tumors than similarly treated heterozygous mice

increased malignant tumor incidence ( J:83967 )

• irradiated mice develop multiple malignant tumors per mouse unlike similarly treated wild-type mice

increased incidence of tumors by ionizing radiation induction ( J:83967 )

• irradiated mice develop more tumors per mouse, 2.2-fold more benign tumors, multiple malignant tumors per mouse, and a broader spectrum of tumors than similarly treated wild-type mice

• irradiated mice develop 2.7-fold more metastatic tumors than similarly treated heterozygous mice

• however, the latency to tumor development and the percent of mice bearing tumors is normal

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:60945 )

• mice receiving serially transplanted bone marrow exhibit decreased survival compared with mice receiving similarly treated wild-type bone marrow

increased susceptibility to xenobiotic induced morbidity/mortality ( J:60945 )

• 5-fluorouracil-treated mice exhibit reduced survival compared with similarly treated wild-type mice

• when bone marrow is used to repopulate irradiated mice that are subsequently treated with 5-FU mice exhibit decreased survival compared with mice repopulated with wild-type bone marrow

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 mice

homeostasis/metabolism

increased DNA replication ( J:59647 )

• STZ-treated mice exhibit an increase in tubular DNA synthesis compared to similarly treated wild-type mice

increased circulating cholesterol level ( J:118516 )

increased susceptibility to xenobiotic induced morbidity/mortality ( J:60945 )

• 5-fluorouracil-treated mice exhibit reduced survival compared with similarly treated wild-type mice

• when bone marrow is used to repopulate irradiated mice that are subsequently treated with 5-FU mice exhibit decreased survival compared with mice repopulated with wild-type bone marrow

decreased physiological sensitivity to xenobiotic ( J:59647 )

• streptozotocin (STZ)-treated mice fail to exhibit proteinuria, glomerular hypertrophy, and an increase in glomerular matrix unlike similarly treated wild-type mice

abnormal response to CNS ischemic injury ( J:90479 )

• 1 week after mid-cerebral artery occlusion (MCAO), proliferation of neural precursor, neural precursor cell numbers, and the number of differentiated neurons are increased compared to in similarly treated wild-type mice

• however, proliferation reverts to baseline 2 weeks after MCAO

cellular

increased sensitivity to induced cell death ( J:85569 )

• mutant MEFs are more sensitive to etoposide, adriamycin, or cisplatin induced apoptosis than wild-type MEFs

increased cellular sensitivity to ultraviolet irradiation ( J:85569 )

• MEFs are highly sensitive to UV-induced apoptosis

abnormal neuronal precursor proliferation ( J:90479 )

• 1 week after mid-cerebral artery occlusion (MCAO), proliferation of neural precursor is increased compared to in similarly treated wild-type mice

• however, proliferation reverts to baseline 2 weeks after MCAO

increased cell proliferation ( J:180692 )

• in mouse embryonic cells

increased DNA replication ( J:59647 )

• STZ-treated mice exhibit an increase in tubular DNA synthesis compared to similarly treated wild-type mice

hematopoietic system

increased hematopoietic stem cell number ( J:60945 )

• under homeostatic condition due to increased stem cell proliferation

abnormal hematopoietic stem cell physiology ( J:60945 )

• under homeostatic condition, hematopoietic stem cell proliferation is increased compared to in wild-type mice

• following repeated transplantation, self-renewal of primitive hematopoietic cells is impaired and leads to hematopoietic failure due to stem cell exhaustion unlike when wild-type bone marrow is used

• however, bone marrow cell homing is normal in serial transplantation experiments

nervous system

abnormal neuronal precursor proliferation ( J:90479 )

• 1 week after mid-cerebral artery occlusion (MCAO), proliferation of neural precursor is increased compared to in similarly treated wild-type mice

• however, proliferation reverts to baseline 2 weeks after MCAO

abnormal response to CNS ischemic injury ( J:90479 )

• however, proliferation reverts to baseline 2 weeks after MCAO

increased brain weight ( J:118516 )

increased neuronal precursor cell number ( J:90479 )

• following mid-cerebral artery occlusion

increased neuron number ( J:90479 )

• following mid-cerebral artery occlusion

adipose tissue

increased brown adipose tissue amount ( J:118516 )

• 38% compared to in wild-type mice

increased white fat cell number ( J:118516 )

• the number of adipocytes in the parametrial fat pad is increased 1.7-fold compared to in wild-type mice

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

• the number of small adipocytes is increased 1.7-fold compared to in wild-type mice

increased inguinal fat pad weight ( J:118516 )

increased parametrial fat pad weight ( J:118516 )

• 90% at 130 days compared to in wild-type mice

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 mice

decreased body weight ( J:102001 )

increased body weight ( J:118516 )

• at 60 to 120 days

increased kidney weight ( J:118516 )

• 18% compared to in wild-type mice

renal/urinary system

increased kidney weight ( J:118516 )

• 18% 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 mice

endocrine/exocrine glands

abnormal prostate gland dorsolateral lobe morphology ( J:115443 )

• prostate gland dorsolateral lobe DNA content is decreased 67% compared to in wild-type mice

decreased prostate gland dorsolateral lobe weight ( J:115443 )

• prostate gland dorsolateral lobe weight is decreased 59% compared to in wild-type mice

decreased seminal vesicle weight ( J:115443 )

• 27% compared to in wild-type mice

reproductive system

abnormal prostate gland dorsolateral lobe morphology ( J:115443 )

• prostate gland dorsolateral lobe DNA content is decreased 67% compared to in wild-type mice

decreased prostate gland dorsolateral lobe weight ( J:115443 )

• prostate gland dorsolateral lobe weight is decreased 59% compared to in wild-type mice

decreased seminal vesicle weight ( J:115443 )

• 27% compared to in wild-type mice

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

mortality/aging

decreased mortality induced by ionizing radiation ( J:70894 )

• irradiated mice survive longer than similarly treated wild-type mice

• irradiated mice do not die from glomerulonephritis

premature death ( J:60292 , J:70894 )

	• mice exhibit premature death mostly due to glomerulonephritis and tumorigenesis (J:70894) • reduced viability is more pronounced in female mice compared to in wild-type mice (J:70894) • however, irradiated mice do not die from glomerulonephritis (J:70894)
	• female, but not male, mice exhibit age-dependent increase in premature death compared with wild-type mice (J:60292)

reproductive system

increased Leydig cell tumor incidence ( J:70894 )

• 1 Leydig cell adenoma and 1 malignant Leydig cell tumor with lung metastasis in 65 mice

immune system

immune system phenotype ( J:60292 )

N	• B cell proliferation is normal

increased T cell proliferation ( J:60292 )

• CD4+ T cell proliferation under conditions of sustained IL2 stimulation is increased compared with similarly treated wild-type cells

• CD4+CD44^high T cells from male mice stimulated with IL2 exhibit increased proliferation compared with wild-type cells

• however, proliferation following initial activation and apoptosis levels are normal

abnormal thymus physiology ( J:70894 )

• following irradiation, thymic lymphomas exhibit an increase in apoptosis compared to in wild-type mice

enlarged spleen ( J:60292 )

• in female, but not male, mice at 9 months

increased spleen weight ( J:60292 )

• in female, but not male, mice

spleen hyperplasia ( J:60292 )

• in female, but not male, mice

increased B cell number ( J:60292 )

• at 9 months, mice exhibit an increase in the proportion of B cells in the lymph node compared to in wild-type mice

increased memory T cell number ( J:60292 )

• at 4 and 9 months, mice exhibit an accumulation of memory/effector CD4+CD44^high T cells in the spleen compared to in wild-type mice

• female mice exhibit a greater increase than male mice

abnormal CD4-positive, alpha beta T cell morphology ( J:60292 )

• at 4 and 9 months, mice exhibit an accumulation of memory/effector CD4+CD44^high T cells in the spleen compared to in wild-type mice

• female mice exhibit a greater increase than male mice

increased IgG1 level ( J:60292 )

• at 9 to 12 months in male and female mice

enlarged lymph nodes ( J:60292 )

• at 6 to 7 months, female mice exhibit a moderate increase in lymph node size compared with wild-type mice

• at 9 months, females and males exhibit dramatic and moderate, respectively, increases in lymph node size and weight compared to in wild-type mice

lymph node hyperplasia ( J:60292 )

enlarged cervical lymph nodes ( J:60292 )

• cervical lymph node weight is increased in male and female mice compared to in wild-type mice

abnormal self tolerance ( J:60292 )

• female, but not male, mice exhibit a loss of tolerance towards nuclear antigens unlike in wild-type mice

increased anti-nuclear antigen antibody level ( J:60292 )

• at 4 months in female, but not male, mice

• at 9 to 12 months in male and female mice

increased anti-double stranded DNA antibody level ( J:60292 )

• older female, but not male, mice exhibit increased levels of IgG2a and IgG3 antibodies against dsDNA compared with wild-type mice

increased anti-histone antibody level ( J:60292 )

• at 9 to 12 months in male and female mice

glomerulonephritis ( J:60292 , J:70894 )

	• in 60% of female mice at an average age of 9.6 months (J:70894) • in 26% of male mice at an average age of 13.2 months (J:70894)
	• age-dependent and severe in female, but not male, mice (J:60292)

respiratory system

increased lung carcinoma incidence ( J:70894 )

• in 3 of 65 mice

neoplasm

decreased incidence of tumors by ionizing radiation induction ( J:70894 )

• only one third of irradiated mice develop tumors (5 T cell lymphomas, 1 hemangiosarcoma, and 1 pituitary carcinoma in 22 mice) compared with 100% of similarly treated wild-type mice

increased tumor incidence ( J:70894 )

• mice exhibit an increased incidence of tumor with an average lifespan of 16 months

increased sebaceous gland adenoma incidence ( J:70894 )

• in 1 of 65 mice

increased Leydig cell tumor incidence ( J:70894 )

• 1 Leydig cell adenoma and 1 malignant Leydig cell tumor with lung metastasis in 65 mice

increased T cell derived lymphoma incidence ( J:70894 )

• in 5 of 22 irradiated mice compared with 7 of 16 irradiated wild-type mice

increased incidence of tumors by chemical induction ( J:80271 )

• treatment with the chemical carcinogen, urethane, results in accelerated tumor onset and increased tumor multiplicity compared to controls; tumors are predominantly lung tumors

increased skin tumor incidence ( J:70894 )

• in 2 of 65 mice (one keratoachantoma and one sebaceous gland adenoma)

increased B cell derived lymphoma incidence ( J:70894 )

• in 9 of 65 mice

increased histiocytic sarcoma incidence ( J:70894 )

• in 34 of 65 mice

increased carcinoma incidence ( J:70894 )

• 1 in 22 irradiated mice develop pituitary carcinoma unlike irradiated wild-type mice

increased lung carcinoma incidence ( J:70894 )

• in 3 of 65 mice

increased hemangiosarcoma incidence ( J:70894 )

• in 14 of 65 mice

• in 1 of 22 irradiated mice compared with 3 of 16 irradiated wild-type mice

increased urinary system tumor incidence ( J:70894 )

• 1 in 65 mice developed an urinary bladder tumor

renal/urinary system

increased urine protein level ( J:60292 )

• in female, but not male, mice

glomerulonephritis ( J:60292 , J:70894 )

	• in 60% of female mice at an average age of 9.6 months (J:70894) • in 26% of male mice at an average age of 13.2 months (J:70894)
	• age-dependent and severe in female, but not male, mice (J:60292)

increased urinary system tumor incidence ( J:70894 )

• 1 in 65 mice developed an urinary bladder tumor

kidney failure ( J:70894 )

• in 60% of female mice at an average age of 9.6 months

• in 26% of male mice at an average age of 13.2 months

homeostasis/metabolism

increased urine protein level ( J:60292 )

• in female, but not male, mice

decreased mortality induced by ionizing radiation ( J:70894 )

• irradiated mice survive longer than similarly treated wild-type mice

• irradiated mice do not die from glomerulonephritis

increased incidence of tumors by chemical induction ( J:80271 )

• treatment with the chemical carcinogen, urethane, results in accelerated tumor onset and increased tumor multiplicity compared to controls; tumors are predominantly lung tumors

hematopoietic system

increased T cell proliferation ( J:60292 )

• CD4+ T cell proliferation under conditions of sustained IL2 stimulation is increased compared with similarly treated wild-type cells

• CD4+CD44^high T cells from male mice stimulated with IL2 exhibit increased proliferation compared with wild-type cells

• however, proliferation following initial activation and apoptosis levels are normal

abnormal thymus physiology ( J:70894 )

• following irradiation, thymic lymphomas exhibit an increase in apoptosis compared to in wild-type mice

enlarged spleen ( J:60292 )

• in female, but not male, mice at 9 months

increased spleen weight ( J:60292 )

• in female, but not male, mice

spleen hyperplasia ( J:60292 )

• in female, but not male, mice

increased B cell number ( J:60292 )

• at 9 months, mice exhibit an increase in the proportion of B cells in the lymph node compared to in wild-type mice

increased memory T cell number ( J:60292 )

• at 4 and 9 months, mice exhibit an accumulation of memory/effector CD4+CD44^high T cells in the spleen compared to in wild-type mice

• female mice exhibit a greater increase than male mice

abnormal CD4-positive, alpha beta T cell morphology ( J:60292 )

• at 4 and 9 months, mice exhibit an accumulation of memory/effector CD4+CD44^high T cells in the spleen compared to in wild-type mice

• female mice exhibit a greater increase than male mice

increased IgG1 level ( J:60292 )

• at 9 to 12 months in male and female mice

cellular

increased cellular sensitivity to gamma-irradiation ( J:70894 )

• following irradiation, thymic lymphomas exhibit an increase in apoptosis compared to in wild-type mice

increased T cell proliferation ( J:60292 )

• CD4+ T cell proliferation under conditions of sustained IL2 stimulation is increased compared with similarly treated wild-type cells

• CD4+CD44^high T cells from male mice stimulated with IL2 exhibit increased proliferation compared with wild-type cells

• however, proliferation following initial activation and apoptosis levels are normal

integument

decreased sensitivity to skin irradiation ( J:114161 )

• following ionizing radiation treatment, arrested cell growth in the epidermis is abrogated compared to in similarly treated wild-type mice

increased skin tumor incidence ( J:70894 )

• in 2 of 65 mice (one keratoachantoma and one sebaceous gland adenoma)

endocrine/exocrine glands

increased sebaceous gland adenoma incidence ( J:70894 )

• in 1 of 65 mice

increased Leydig cell tumor incidence ( J:70894 )

• 1 Leydig cell adenoma and 1 malignant Leydig cell tumor with lung metastasis in 65 mice

increased T cell derived lymphoma incidence ( J:70894 )

• in 5 of 22 irradiated mice compared with 7 of 16 irradiated wild-type mice

abnormal thymus physiology ( J:70894 )

• following irradiation, thymic lymphomas exhibit an increase in apoptosis compared to in wild-type mice

growth/size/body

enlarged spleen ( J:60292 )

• in female, but not male, mice at 9 months

increased spleen weight ( J:60292 )

• in female, but not male, mice

spleen hyperplasia ( J:60292 )

• in female, but not male, mice

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

cellular

abnormal cell physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type cells indicating increased tumorgenicity

delayed cellular replicative senescence ( J:72780 )

• age-related senescence in the epidermis in vivo is moderately decreased compared to in wild-type mice

neoplasm

increased squamous cell carcinoma incidence ( J:72780 )

• 1 of 6 nude mice transplanted with keratinocytes infected with a vHaras-expressing retrovirus develop well differentiated SCCs unlike nude mice receiving similarly treated wild-type cells

integument

abnormal skin physiology ( J:72780 )

• age-related senescence in the epidermis in vivo is moderately decreased compared to in wild-type mice

abnormal keratinocyte physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type cells indicating increased tumorgenicity

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a⁺
Genetic Background	involves: 129S1/SvImJ * 129S2/SvPas * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

neoplasm

increased malignant tumor incidence ( J:83967 )

• irradiated mice develop multiple malignant tumors per mouse unlike similarly treated wild-type mice

increased incidence of tumors by ionizing radiation induction ( J:83967 )

• irradiated mice develop more tumors per mouse, 2.2-fold more benign tumors, multiple malignant tumors per mouse, and a broader spectrum of tumors than similarly treated wild-type mice

• however, the latency to tumor development and the percent of mice bearing tumors is normal

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0
Genetic Background	involves: 129 * C57BL/6 * CD-1 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Csnk1a1^tm1.1Ybn mutation (1 available); any Csnk1a1 mutation (38 available)
Tg(Vil1-cre/ERT2)23Syr mutation (1 available)

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

neoplasm

increased carcinoma incidence ( J:204886 )

• tamoxifen-treated mice exhibit severe dysplasia and intramucosal carcinomas throughout the small bowel

digestive/alimentary system

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

cellular

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

Allelic Composition	Brca1^tm2Mak/Brca1^tm2Mak Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(Lck-cre)548Jxm/?
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Brca1^tm2Mak mutation (1 available); any Brca1 mutation (113 available)
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Tg(Lck-cre)548Jxm mutation (2 available)

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

immune system

immune system phenotype ( J:63282 )

N	• T cell numbers in lymph nodes are more nearly normal

decreased thymocyte number ( J:63282 )

hematopoietic system

decreased thymocyte number ( J:63282 )

endocrine/exocrine glands

decreased thymocyte number ( J:63282 )

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Pten^tm1Hwu/Pten^tm1Hwu Tg(Fabp1-cre)1Jig/0
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Pten^tm1Hwu mutation (16 available); any Pten mutation (86 available)
Tg(Fabp1-cre)1Jig mutation (2 available)

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

renal/urinary system

increased urinary bladder carcinoma incidence ( J:106662 )

abnormal urinary bladder urothelium morphology ( J:106662 )

• bladder urothelium exhibits increased cell proliferation

neoplasm

increased urinary bladder carcinoma incidence ( J:106662 )

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Itgb1^tm1Mll/Itgb1^tm1Mll Tg(Wap-cre)1Gsc/0
Genetic Background	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Itgb1^tm1Mll mutation (1 available); any Itgb1 mutation (59 available)
Tg(Wap-cre)1Gsc mutation (1 available)

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

endocrine/exocrine glands

abnormal mammary gland growth during lactation ( J:99405 )

• mutants show a decrease in cell proliferation in mammary glands compared to wild-type, however they show a significant increase in cell proliferation compared to the conditional Itgb1 mutant glands, which represents a partial, 55%, reversion of the phenotype

integument

abnormal mammary gland growth during lactation ( J:99405 )

Allelic Composition	Apoe^tm1Unc/Apoe^tm1Unc Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	B6.129-Apoe^tm1Unc Cdkn1a^tm1Tyj

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^tm1Unc mutation (33 available); any Apoe mutation (152 available)
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:125247 )

• angiotensin II-treated mice exhibit less of an increase in mortality compared with similarly treated Apoe^tm1Unc homozygotes

cardiovascular system

decreased susceptibility to atherosclerosis ( J:125247 )

• angiotensin II-treated mice exhibit a smaller increase in plaque area, plaque grade, aortic aneurysms, atheroma, and mortality but an increase in proliferation of vascular smooth muscle cells compared with similarly treated Apoe^tm1Unc homozygotes

abnormal vascular smooth muscle physiology ( J:125247 )

• treatment with angiotensin II induces less vascular smooth muscle cell senescence and more proliferation compared to in similarly treated Apoe^tm1Unc homozygotes

increased vascular smooth muscle cell proliferation ( J:125247 )

• treatment with angiotensin II induces more vascular smooth muscle proliferation compared to in similarly treated Apoe^tm1Unc homozygotes

homeostasis/metabolism

abnormal response/metabolism to endogenous compounds ( J:125247 )

• angiotensin II-treated mice exhibit a smaller increase in plaque area, plaque grade, aortic aneurysms, atheroma, and mortality but an increase in proliferation and decrease in senescence of vascular smooth muscle cells compared with similarly treated Apoe^tm1Unc homozygotes

cellular

increased vascular smooth muscle cell proliferation ( J:125247 )

• treatment with angiotensin II induces more vascular smooth muscle proliferation compared to in similarly treated Apoe^tm1Unc homozygotes

delayed cellular replicative senescence ( J:125247 )

• treatment with angiotensin II induces less vascular smooth muscle cell senescence compared to in similarly treated Apoe^tm1Unc homozygotes

muscle

abnormal vascular smooth muscle physiology ( J:125247 )

• treatment with angiotensin II induces less vascular smooth muscle cell senescence and more proliferation compared to in similarly treated Apoe^tm1Unc homozygotes

increased vascular smooth muscle cell proliferation ( J:125247 )

• treatment with angiotensin II induces more vascular smooth muscle proliferation compared to in similarly treated Apoe^tm1Unc homozygotes

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Gadd45a^tm1Ajf/Gadd45a^tm1Ajf
Genetic Background	either: (involves: 129P2/OlaHsd) or (involves: 129X1/SvJ)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Gadd45a^tm1Ajf mutation (2 available); any Gadd45a mutation (15 available)

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

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:101710 )

• UV-irradiated keratinocytes do not undergo apoptosis unlike keratinocytes from Gadd45a^tm1Ajf homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:101710 )

N	• UV-irradiated keratinocytes exhibit normal nucleotide excision repair

Allelic Composition	Brca1^tm1Mak/Brca1^tm1Mak Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Brca1^tm1Mak mutation (0 available); any Brca1 mutation (113 available)
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:41254 )

• mice die between E9.5 and E11.5

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2d^tm1Maro/Cdkn2d^tm1Maro
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * 129X1/SvJ * C57BL/6 * CD-1

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Cdkn2d^tm1Maro mutation (1 available); any Cdkn2d mutation (25 available)

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

hearing/vestibular/ear

decreased cochlear hair cell number ( J:118337 )

• loss of hair cells is more severe than in Cdkn2d^tm1Maro homozygotes

• however, vestibular hair cells are not lost

decreased cochlear outer hair cell number ( J:118337 )

• at P5, mice exhibit a 5% loss of outer hair cells by apoptosis

• at 2 months, mice exhibit a 87% loss of outer hair cells overall, a 62% loss in the basal region, and a 26% loss in the apical region

increased cochlear hair cell number ( J:118337 )

• mice exhibit a transient increase in hair cells

abnormal cochlear inner hair cell morphology ( J:118337 )

• inner nuclear hair cells exhibit abnormal nuclear morphology with a low frequency of polyploidy unlike in wild-type mice

decreased cochlear inner hair cell number ( J:118337 )

• at P5, mice exhibit a 2.5% loss of inner hair cells by apoptosis

• at 2 months, mice exhibit a 66% loss of inner hair cells overall, a 64% loss in the basal region, and a 26% loss in the apical region

abnormal cochlear hair cell physiology ( J:118337 )

• at P3 and P6, auditory hair cells exhibit increased proliferation as measured by S-phase reentry compared to in Cdkn2d^tm1Maro homozyogtes

• proliferation of hair cells increases by P6 but drops off after P10

• increased hair cell proliferation is followed by DNA damage and apoptosis

cellular

polyploidy ( J:118337 )

• inner nuclear hair cells exhibit abnormal nuclear morphology with a low frequency of polyploidy unlike in wild-type mice

nervous system

decreased cochlear hair cell number ( J:118337 )

• loss of hair cells is more severe than in Cdkn2d^tm1Maro homozygotes

• however, vestibular hair cells are not lost

decreased cochlear inner hair cell number ( J:118337 )

• at P5, mice exhibit a 2.5% loss of inner hair cells by apoptosis

• at 2 months, mice exhibit a 66% loss of inner hair cells overall, a 64% loss in the basal region, and a 26% loss in the apical region

decreased cochlear outer hair cell number ( J:118337 )

• at P5, mice exhibit a 5% loss of outer hair cells by apoptosis

• at 2 months, mice exhibit a 87% loss of outer hair cells overall, a 62% loss in the basal region, and a 26% loss in the apical region

increased cochlear hair cell number ( J:118337 )

• mice exhibit a transient increase in hair cells

abnormal cochlear inner hair cell morphology ( J:118337 )

• inner nuclear hair cells exhibit abnormal nuclear morphology with a low frequency of polyploidy unlike in wild-type mice

abnormal cochlear hair cell physiology ( J:118337 )

• at P3 and P6, auditory hair cells exhibit increased proliferation as measured by S-phase reentry compared to in Cdkn2d^tm1Maro homozyogtes

• proliferation of hair cells increases by P6 but drops off after P10

• increased hair cell proliferation is followed by DNA damage and apoptosis

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Cdkn1b^tm1Ako mutation (0 available); any Cdkn1b mutation (26 available)

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

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

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Gata1^tm1.1Yen/Gata1^tm1.1Yen
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Gata1^tm1.1Yen mutation (0 available); any Gata1 mutation (44 available)

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

hematopoietic system

hematopoietic system phenotype ( J:200716 )

N	• the number of colony forming erythroid cells is rescued

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Zfpm2^tm1.1Esv/Zfpm2^tm1.1Esv
Genetic Background	involves: 129S1/SvImJ * 129S2/SvPas * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Zfpm2^tm1.1Esv mutation (0 available); any Zfpm2 mutation (47 available)

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

muscle

abnormal myocardium compact layer morphology ( J:216295 )

• at birth, double homozygotes display a significantly thicker myocardial compact zone than single Zfpm2^tm1.1Esv homozygotes; however, left ventricular wall thickness is still not completely normal

mortality/aging

postnatal lethality, complete penetrance ( J:216295 )

• double homozygotes die by P14, possibly due to septal defects

cardiovascular system

abnormal myocardium compact layer morphology ( J:216295 )

atrial septal defect ( J:216295 )

• atrial septal defects are still present at P0

ventricular septal defect ( J:216295 )

• ventricular septal defects are still present at P0

abnormal heart left ventricle wall thickness ( J:216295 )

• at birth, double homozygotes show only a modest 26.8 +/- 3.2% rescue of left ventricular wall thickness relative to wild-type controls

• however, left ventricular fractional shortening is preserved, indicating that increased wall thickness improves left ventricular function

abnormal heart echocardiography feature ( J:216295 )

• at P0, echocardiographic M-mode tracings revealed a slight increase in left ventricular end diastolic dimension (LVEDD) relative to wild-type controls, suggesting that mutant hearts are starting to dilate and fail

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1⁺ Tg(Rb1)1Blg/0
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Rb1^tm1Tyj mutation (5 available); any Rb1 mutation (107 available)
Tg(Rb1)1Blg mutation (0 available)

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

skeleton

abnormal xiphoid process morphology ( J:65679 )

• at E17.5

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg/0
Genetic Background	involves: 129S2/SvPas

Find Mice

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

skeleton

abnormal deltoid tuberosity morphology ( J:65679 )

• less developed in some mice

absent deltoid tuberosity ( J:65679 )

• in some mice

decreased length of long bones ( J:65679 )

• compared with Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal scapula morphology ( J:65679 )

• at E16.5, the scapula is brittle and perforated with unclear boundaries between bone and cartilage compared to in heterozygous mice

abnormal sternocostal joint morphology ( J:65679 )

• at E17.5, ribs join the sternim at a 90 degree angle unlike in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

abnormal sternum ossification ( J:65679 )

• at E17.5

abnormal xiphoid process morphology ( J:65679 )

• at E17.5

fragile skeleton ( J:65679 )

muscle

abnormal myogenesis ( J:65679 )

• at E16.5, myotomes undergo nuclei catastrophe and exhibit increased apoptosis compared to in single homozygotes

abnormal skeletal muscle fiber morphology ( J:65679 )

• at E16.5 to E18.5, myotubes exhibit increased nuclear content compared with wild-type myotubes

• at E16.5, myotubes are shorter and more disorganize than in single homozygotes

abnormal muscle physiology ( J:65679 )

• at E16.5, skeletal muscle exhibit an increase in apoptosis compared with Cdkn1a^tm1Tyj/Cdkn1a⁺ Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

behavior/neurological

abnormal posture ( J:65679 )

• more severe than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

hunched posture ( J:65679 )

• more severe than in Rb1^tm1Tyj/Rb1^tm1Tyj Tg(Rb1)1Blg mice

cardiovascular system

hemorrhage ( J:65679 )

• at E18.5, embryos exhibit patches of hemorrhage unlike wild-type mice

cellular

polyploidy ( J:65679 )

• at E16.5 to E18.5, myotubes exhibit increased nuclear content compared with wild-type myotubes

limbs/digits/tail

abnormal deltoid tuberosity morphology ( J:65679 )

• less developed in some mice

absent deltoid tuberosity ( J:65679 )

• in some mice

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Foxk1^tm1Djg/Foxk1^tm1Djg
Genetic Background	involves: 129S2/SvPas * 129S4/SvJae

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Foxk1^tm1Djg mutation (0 available); any Foxk1 mutation (29 available)

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

cellular

cellular phenotype ( J:81688 )

N	• G₀/G₁ arrest of cell cycle is prevented

growth/size/body

growth/size/body region phenotype ( J:81688 )

N	• growth retardation is prevented • there is no significant size difference from controls

muscle

muscle phenotype ( J:81688 )

N	• no impairment in skeletal muscle regeneration is observed

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf
Genetic Background	involves: 129S2/SvPas * 129S4/SvJaeSor

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Cdkn1b^tm1Mlf mutation (2 available); any Cdkn1b mutation (26 available)

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

digestive/alimentary system

abnormal enterocyte proliferation ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in enterocyte proliferation unlike similarly treated wild-type mice

abnormal crypts of Lieberkuhn morphology ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in crypt depth unlike similarly treated wild-type mice

abnormal ileum morphology ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in ileal weight unlike similarly treated wild-type mice

abnormal small intestinal villus morphology ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in villus height unlike similarly treated wild-type mice

homeostasis/metabolism

abnormal response to injury ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in ileal weight, villus height, crypt depth, or enterocyte proliferation unlike similarly treated wild-type mice

• however, increase in enterocyte apoptosis following SBR is normal

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in crypt depth unlike similarly treated wild-type mice

cellular

abnormal enterocyte proliferation ( J:111081 )

• following small bowel resection (SBR), mice fail to exhibit an increase in enterocyte proliferation unlike similarly treated wild-type mice

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Palb2^tm1.2Dli/Palb2^tm1.2Dli
Genetic Background	involves: 129S2/SvPas * 129S4/SvJaeSor * BALB/cJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Palb2^tm1.2Dli mutation (0 available); any Palb2 mutation (50 available)

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:197442 )

• lethality observed in Palb2^tm1.2Dli homozygotes is delayed 2 to 3 days

growth/size/body

fetal growth retardation ( J:197442 )

embryo

abnormal embryo development ( J:197442 )

• multiple malformations

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Fah^tm1Mgo/Fah^tm1Mgo
Genetic Background	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Fah^tm1Mgo mutation (0 available); any Fah mutation (36 available)

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

mortality/aging

mortality/aging ( J:138701 )

N	• mice survive NTBC withdrawal unlike similarly treated Fah^tm1Mgo homozygotes

neoplasm

increased hepatocellular carcinoma incidence ( J:138701 )

• 7 to 8 weeks following NTBC withdrawal and 8 weeks following low-dose NTBC treatment, mice develop hepatocellular carcinomas unlike similarly treated Fah^tm1Mgo homozygotes

• tumors that develop following treatment with low-dose NTBC are smaller and fewer than those in mice following complete withdrawal of NTBC

increased renal carcinoma incidence ( J:138701 )

• in 80% of mice 12 weeks after NTBC withdrawal

liver/biliary system

abnormal hepatocyte morphology ( J:138701 )

• following NTBC withdrawal, hepactocytes are dysplastic with increased DNA damage compared with cells from similarly treated Fah^tm1Mgo homozygotes

increased hepatocellular carcinoma incidence ( J:138701 )

• 7 to 8 weeks following NTBC withdrawal and 8 weeks following low-dose NTBC treatment, mice develop hepatocellular carcinomas unlike similarly treated Fah^tm1Mgo homozygotes

• tumors that develop following treatment with low-dose NTBC are smaller and fewer than those in mice following complete withdrawal of NTBC

abnormal liver physiology ( J:138701 )

• following NTBC withdrawal, hepatocytes exhibit increased DNA damage compared with similarly treated cells from Fah^tm1Mgo homozygotes

increased hepatocyte apoptosis ( J:138701 )

• following NTBC withdrawal

increased hepatocyte proliferation ( J:138701 )

• following NTBC withdrawal unlike in similarly treated Fah^tm1Mgo homozygotes

renal/urinary system

kidney cyst ( J:138701 )

• 10 weeks after NTBC withdrawal, mice develop macroscopic cysts comprised of renal parenchyma unlike similarly treated Fah^tm1Mgo homozygotes

increased renal carcinoma incidence ( J:138701 )

• in 80% of mice 12 weeks after NTBC withdrawal

dilated proximal convoluted tubule ( J:138701 )

• following NTBC withdrawal

growth/size/body

weight loss ( J:138701 )

• following NTBC withdrawal, mice exhibit weight loss with a plateau at 5 and 6 weeks after withdrawal compared with similarly treated Fah^tm1Mgo homozygotes

kidney cyst ( J:138701 )

• 10 weeks after NTBC withdrawal, mice develop macroscopic cysts comprised of renal parenchyma unlike similarly treated Fah^tm1Mgo homozygotes

cellular

increased hepatocyte apoptosis ( J:138701 )

• following NTBC withdrawal

increased hepatocyte proliferation ( J:138701 )

• following NTBC withdrawal unlike in similarly treated Fah^tm1Mgo homozygotes

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Mir34a^tm1.1Lhe/Mir34a^tm1.1Lhe
Genetic Background	involves: 129S2/SvPas * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Mir34a^tm1.1Lhe mutation (1 available); any Mir34a mutation (9 available)

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

cellular

abnormal cell physiology ( J:180692 )

• induced mouse embryonic fibroblasts exhibit an increase in reprogramming efficiency and generation of induced pluripotent stem cell compared with wild-type and Mir34a^tm1.1Ghan cells

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(MMTV-vHaras)SH1Led/0
Genetic Background	involves: 129S2/SvPas * C57BL/6J * CD-1 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Tg(MMTV-vHaras)SH1Led mutation (1 available)

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

neoplasm

increased tumor incidence ( J:66183 )

• exhibit increased tumor multiplicity and aggressiveness, however, once tumors appear, their growth rate, apoptosis level, and mitotic index are not affected

increased salivary adenocarcinoma incidence ( J:66183 )

• by 63 days of age, all mice develop either malignant (mammary and/or salivary adenocarcinomas) or benign (Harderian hyperplasia) tumors, compared to only 1 of 9 controls expressing only the Tg(MMTV-vHaras)SH1Led transgene

increased mammary adenocarcinoma incidence ( J:66183 )

• by 94 days of age, 50% develop mammary tumors compared to none of the controls

• by 4 months of age, the mammary tumor multiplicity is 10-fold greater than in controls

decreased tumor latency ( J:66183 )

• exhibit earlier onset of tumors

endocrine/exocrine glands

increased salivary adenocarcinoma incidence ( J:66183 )

increased mammary adenocarcinoma incidence ( J:66183 )

• by 94 days of age, 50% develop mammary tumors compared to none of the controls

• by 4 months of age, the mammary tumor multiplicity is 10-fold greater than in controls

enlarged Harderian gland ( J:66183 )

• enlargement of the glands is evident as early as 5 weeks after birth, with glands reaching up to 20 times their normal weight by 4 months of age

Harderian gland hyperplasia ( J:66183 )

• 100% of mutants exhibit bilateral hyperplasia of the Harderian lacrimal glands by 63 days of age

hematopoietic system

enlarged spleen ( J:66183 )

• splenomegaly is due to a moderate to marked extramedullary hematopoiesis

extramedullary hematopoiesis ( J:66183 )

• extramedullary hematopoiesis, frequently displaying atypical lymphoid cells and megakariocytes, results in splenomegaly

immune system

enlarged spleen ( J:66183 )

• splenomegaly is due to a moderate to marked extramedullary hematopoiesis

digestive/alimentary system

increased salivary adenocarcinoma incidence ( J:66183 )

integument

increased mammary adenocarcinoma incidence ( J:66183 )

• by 94 days of age, 50% develop mammary tumors compared to none of the controls

• by 4 months of age, the mammary tumor multiplicity is 10-fold greater than in controls

growth/size/body

enlarged spleen ( J:66183 )

• splenomegaly is due to a moderate to marked extramedullary hematopoiesis

Allelic Composition	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp
Genetic Background	involves: 129/Sv * 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1a^tm1Tyj mutation (3 available); any Cdkn1a mutation (60 available)
Cdkn2a^tm1Rdp mutation (6 available); any Cdkn2a mutation (64 available)

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

cellular

abnormal cell physiology ( J:72780 )

• vHaras-induced foci formation in primary keratinocytes is increased compared with similarly treated wild-type and single homozygous cells indicating increased tumorgenicity

increased keratinocyte proliferation ( J:72780 )

• keratinocyte proliferation is increased compared to in wild-type cells

delayed cellular replicative senescence ( J:72780 )

• age-related senescence in the epidermis in vivo is almost absent compared to in wild-type mice

• vHaras-induced premature senescence of primary keratinocytes is decreased compared with similarly treated wild-type cells

• however, calcium- and Tgfb-induced cell growth arrest is normal

neoplasm

increased squamous cell carcinoma incidence ( J:72780 )

• 2 tumors are observed when keratinocytes are transplanted into nude mice unlike when wild-type cells are used

• all nude mice transplanted with keratinocytes infected with a vHaras-expressing retrovirus develop poorly differentiated SCCs with spindle cell morphology unlike nude mice receiving similarly treated wild-type cells

integument

abnormal skin development ( J:72780 )

• mice exhibit altered expression of several markers of epidermis differentiation compared with wild-type mice

abnormal skin physiology ( J:72780 )

• age-related senescence in the epidermis in vivo is almost absent compared to in wild-type mice

abnormal keratinocyte physiology ( J:72780 )

• as determined by marker expression, in vitro keratinocyte differentiation is altered compared with similarly treated cells from wild-type mice and single homozygotes

• vHaras-induced premature senescence of primary keratinocytes is decreased while foci formation is increased compared with similarly treated wild-type cells and single homozygous

• however, calcium- and Tgfb-induced cell growth arrest is normal

increased keratinocyte proliferation ( J:72780 )

• keratinocyte proliferation is increased compared to in wild-type cells

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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