Phenotypes Associated with This Genotype

Genotype
MGI:3706343

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

• ♀: 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

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

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 T cell derived lymphoma incidence ( J:70894 )

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

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 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 cellular sensitivity to gamma-irradiation induced cell death ( J:70894 )

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

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

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 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

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

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 induced cell death ( 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

increased sebaceous gland adenoma incidence ( J:70894 )

• in 1 of 65 mice

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 T cell derived lymphoma incidence ( J:70894 )

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

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

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