All Phenotypes Cdkn2c<tm1Bbd> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd	involves: 129S1/Sv * C57BL/6	MGI:2175773
cn2	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Trp53^tm1Brn/Trp53^tm1Tyj Tg(Nes-cre)1Kln/0	involves: 129P2/OlaHsd * 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL	MGI:3710322
cx3	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Cdkn2d^tm1Maro/Cdkn2d^tm1Maro	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:2662523
cx4	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1⁺	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ	MGI:3710324
cx5	Cdkn2c^tm1Bbd/Cdkn2c⁺ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:3710320
cx6	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:3710321
cx7	Cdkn2c^tm1Bbd/Cdkn2c⁺ Trp53^tm1Tyj/Trp53⁺	involves: 129S1/Sv * 129S2/SvPas * C57BL/6	MGI:3710319
cx8	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5544756
cx9	Cdkn2b^tm1Bbd/Cdkn2b^tm1Bbd Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd	involves: 129S1/Sv * C57BL/6	MGI:2662500

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

mortality/aging

decreased tumor-free survival time ( J:63299 )

• about 40% die before 18 months of age due to large pituitary tumors

neoplasm

neoplasm ( J:102702 )

N	• mice irradiated with 4 Gy at P5 or P6 do not develop cerebellar tumors

increased pheochromocytoma incidence ( J:63299 )

• 10% incidence of pheochromocytomas

increased pituitary adenoma incidence ( J:63299 )

• most large pituitary tumors are chromophobe adenomas of the pars intermedia

increased testis tumor incidence ( J:63299 )

• 12% incidence of testicular neoplasia

increased T cell derived lymphoma incidence ( J:63299 )

• low incidence of thymic lymphoma

increased B cell derived lymphoma incidence ( J:63299 )

• low incidence of B-cell lymphoma

increased renal carcinoma incidence ( J:63299 )

• low incidence of renal cell carcinoma

increased hemangiosarcoma incidence ( J:63299 )

• low incidence of angiosarcoma

endocrine/exocrine glands

pituitary gland hyperplasia ( J:63299 )

• seen as early as 6 months of age

abnormal mammary gland epithelium morphology ( J:63299 )

• cysts in the galactophor ducts of the mammary epithelium at 12 weeks of age

mammary gland hyperplasia ( J:63299 )

abnormal Leydig cell differentiation ( J:68829 )

• failure to differentiate, not associated with abnormal levels of luteinizing hormone (LH)

enlarged testis ( J:68829 )

increased Leydig cell number ( J:68829 )

increased pheochromocytoma incidence ( J:63299 )

• 10% incidence of pheochromocytomas

increased pituitary adenoma incidence ( J:63299 )

• most large pituitary tumors are chromophobe adenomas of the pars intermedia

increased testis tumor incidence ( J:63299 )

• 12% incidence of testicular neoplasia

increased T cell derived lymphoma incidence ( J:63299 )

• low incidence of thymic lymphoma

growth/size/body

kidney cyst ( J:63299 )

• tubular and glomerular cysts

kidney cortex cyst ( J:63299 )

increased body size ( J:63299 )

increased body weight ( J:63299 )

• weight about 20% more than wild-type mice

enlarged spleen ( J:63299 )

• evident after 6 months of age

hematopoietic system

enlarged spleen ( J:63299 )

• evident after 6 months of age

increased spleen white pulp amount ( J:63299 )

• cellular expansion of the white pulp

immune system

enlarged spleen ( J:63299 )

• evident after 6 months of age

increased spleen white pulp amount ( J:63299 )

• cellular expansion of the white pulp

abnormal lymph node medulla morphology ( J:63299 )

• cellular expansion of plasma cells in the medulla

enlarged lymph nodes ( J:63299 )

lymphoid hyperplasia ( J:63299 )

• lymphoproliferative expansion, most often seen in the kidneys, lung, liver, and salivary glands

nervous system

abnormal neuron differentiation ( J:102702 )

• GNPs from mutants show ~50% levels of proliferation compared to Cdkn2c, Trp53-double null cells after 3 days in culture and levels of cells incorporating BrdU are still less in single mutants in tests where cells are stimulated with Shh after culture

abnormal neuronal migration ( J:102702 )

• presence of these aberrant foci cerebellar molecular layer in mutants indicates a migration defect

pituitary gland hyperplasia ( J:63299 )

• seen as early as 6 months of age

increased pituitary adenoma incidence ( J:63299 )

• most large pituitary tumors are chromophobe adenomas of the pars intermedia

abnormal cerebellar molecular layer ( J:102702 )

• when irradiated mice are sacrificed at 6 months of age, all mice have abnormal microscopic foci of neuronal cells that are positive for GABA(A) alpha6 receptor subunit, a marker of differentiated, post-mitotic granule neurons which is not seen in granule neuronal precursor cells; these cells are not proliferating

• when mice are exposed to 4 Gy at P5 and sacrificed at P30, all show ~3-fold more neuronal foci (neuronal nests) located more deeply in the molecular layer compared to few detected accumulating at the external surface of the molecular layer in treated wild type

reproductive system

abnormal Leydig cell differentiation ( J:68829 )

• failure to differentiate, not associated with abnormal levels of luteinizing hormone (LH)

enlarged testis ( J:68829 )

increased Leydig cell number ( J:68829 )

increased testis tumor incidence ( J:63299 )

• 12% incidence of testicular neoplasia

renal/urinary system

kidney cyst ( J:63299 )

• tubular and glomerular cysts

kidney cortex cyst ( J:63299 )

increased renal carcinoma incidence ( J:63299 )

• low incidence of renal cell carcinoma

cortical renal glomerulopathies ( J:63299 )

• about 30% of mutants show cortical glomerulopathies after 9 months of age

• atropic glomeruli and glomerular cysts are sometimes seen

cellular

abnormal apoptosis ( J:68829 )

• increased germ cell apoptosis

abnormal neuron differentiation ( J:102702 )

abnormal neuronal migration ( J:102702 )

• presence of these aberrant foci cerebellar molecular layer in mutants indicates a migration defect

homeostasis/metabolism

decreased circulating testosterone level ( J:68829 )

• ~75% reduction in levels relative to wild-type

• associated with a failure of leydig cell differentiation

integument

abnormal mammary gland epithelium morphology ( J:63299 )

• cysts in the galactophor ducts of the mammary epithelium at 12 weeks of age

mammary gland hyperplasia ( J:63299 )

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Trp53^tm1Brn/Trp53^tm1Tyj Tg(Nes-cre)1Kln/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129S2/SvPas * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2c^tm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)
Tg(Nes-cre)1Kln mutation (4 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (232 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (232 available)

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

neoplasm

increased medulloblastoma incidence ( J:102702 )

• 4/4 of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age

nervous system

increased medulloblastoma incidence ( J:102702 )

• 4/4 of mice receiving 4 Gy radiation at P5 develop cerebellar tumors by 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:102702

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Cdkn2d^tm1Maro/Cdkn2d^tm1Maro
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2c^tm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)
Cdkn2d^tm1Maro mutation (1 available); any Cdkn2d mutation (25 available)

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

neoplasm

increased pheochromocytoma incidence ( J:68829 )

increased pituitary adenoma incidence ( J:68829 )

reproductive system

abnormal germ cell morphology ( J:68829 )

• germ cell apoptosis

decreased germ cell number ( J:68829 )

• germ cell apoptosis

oligozoospermia ( J:68829 )

• 85% decrease in epididymal sperm counts relative to wild-type at 10 and 14 weeks of age

• severely reduced amount of epididymal sperm observed at 6 months of age

asthenozoospermia ( J:68829 )

seminiferous tubule degeneration ( J:68829 )

• atrophic seminiferous tubules

abnormal Leydig cell differentiation ( J:68829 )

• failure to differentiate, not associated with abnormal levels of luteinizing hormone (LH)

increased Leydig cell number ( J:68829 )

• evident at 3 months of age and increased at 6 months

• more severe than leydig hyperplasia observed in Cdkn2c^tm1Bbd

testicular atrophy ( J:68829 )

• atrophy of the testes was more severe than in Cdkn2d^tm1Maro homozygotes

abnormal spermatogenesis ( J:68829 )

• reduced sperm production

abnormal male meiosis ( J:68829 )

• meiotic delay leading to apoptosis

male infertility ( J:68829 )

growth/size/body

increased body weight ( J:68829 )

• increased relative to wild-type and Cdkn2d^tm1Maro homozygous mice

• the weight of females was 92% that of Cdkn2c^tm1Bbd homozygous females

• the weight of males was equal to that of Cdkn2c^tm1Bbd homozygous males

homeostasis/metabolism

decreased circulating testosterone level ( J:68829 )

• 75% reduction in levels relative to wild-type

• associated with a failure of leydig cell differentiation

increased circulating follicle stimulating hormone level ( J:68829 )

endocrine/exocrine glands

seminiferous tubule degeneration ( J:68829 )

• atrophic seminiferous tubules

abnormal Leydig cell differentiation ( J:68829 )

• failure to differentiate, not associated with abnormal levels of luteinizing hormone (LH)

increased Leydig cell number ( J:68829 )

• evident at 3 months of age and increased at 6 months

• more severe than leydig hyperplasia observed in Cdkn2c^tm1Bbd

testicular atrophy ( J:68829 )

• atrophy of the testes was more severe than in Cdkn2d^tm1Maro homozygotes

increased pheochromocytoma incidence ( J:68829 )

increased pituitary adenoma incidence ( J:68829 )

nervous system

increased pituitary adenoma incidence ( J:68829 )

cellular

abnormal germ cell morphology ( J:68829 )

• germ cell apoptosis

decreased germ cell number ( J:68829 )

• germ cell apoptosis

oligozoospermia ( J:68829 )

• 85% decrease in epididymal sperm counts relative to wild-type at 10 and 14 weeks of age

• severely reduced amount of epididymal sperm observed at 6 months of age

abnormal male meiosis ( J:68829 )

• meiotic delay leading to apoptosis

asthenozoospermia ( J:68829 )

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1⁺
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2c^tm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)
Ptch1^tm1Mps mutation (2 available); any Ptch1 mutation (115 available)

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

nervous system

abnormal neuron differentiation ( J:102702 )

• granule neuronal precursors (GNPs) show enhanced proliferation after stimulation with Shh in culture relative to Ptch1 heterozygous, Cdkn2c wild-type cerebellar cells isolated at P10

increased medulloblastoma incidence ( J:102702 )

• mice exhibit earlier onset of tumor formation with greatly increased incidence compared to Ptch1 heterozygotes

neoplasm

increased medulloblastoma incidence ( J:102702 )

• mice exhibit earlier onset of tumor formation with greatly increased incidence compared to Ptch1 heterozygotes

cellular

abnormal neuron differentiation ( J:102702 )

• granule neuronal precursors (GNPs) show enhanced proliferation after stimulation with Shh in culture relative to Ptch1 heterozygous, Cdkn2c wild-type cerebellar cells isolated at P10

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:102702

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c⁺ Trp53^tm1Tyj/Trp53^tm1Tyj
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2c^tm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)
Trp53^tm1Tyj mutation (12 available); any Trp53 mutation (232 available)

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

neoplasm

increased medulloblastoma incidence ( J:102702 )

• 15/17 (88%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

nervous system

increased medulloblastoma incidence ( J:102702 )

• 15/17 (88%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:102702

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Trp53^tm1Tyj/Trp53^tm1Tyj
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * C57BL/6

Find Mice

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

nervous system

abnormal neuron differentiation ( J:102702 )

• lack of Cdkn2c results in earler evidence of tumor formation, shown by increased neuronal proliferation in cerebellum molecular layer, compared to Cdkn2c-sufficient mice mutants

• in 1-month old mutants injected in the cerebella with BrdU, analysis 9 hours post-injection shows proliferating cells in the superficial molecular layer and the internal granule layer while proliferation has ceased in wild-type cerebella

• there is 3-fold increase in proliferating cells relative to control cerebella

• 50% of double null granule neuronal precursor cells (GNPs) from P12 mice show proliferative capacity compared to wild-type cells (in absence of Shh in culture medium); wild-type cells from P7 mice have mostly exited the cell cycle after 3 days in culture, while many double-null cells continue to incorporate BrdU

• in culture, labeled wild-type cells from P10 and 12 mice that are exposed to Shh show greatly reduced BrdU incorporation compared to double-null cells after 72 hours

increased medulloblastoma incidence ( J:102702 )

• 18/24 (75%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

neoplasm

increased medulloblastoma incidence ( J:102702 )

• 18/24 (75%) of animals receiving 4 Gy radiation at P5 or 6 develop cerebellar tumors

cellular

abnormal neuron differentiation ( J:102702 )

• lack of Cdkn2c results in earler evidence of tumor formation, shown by increased neuronal proliferation in cerebellum molecular layer, compared to Cdkn2c-sufficient mice mutants

• there is 3-fold increase in proliferating cells relative to control cerebella

• in culture, labeled wild-type cells from P10 and 12 mice that are exposed to Shh show greatly reduced BrdU incorporation compared to double-null cells after 72 hours

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
medulloblastoma		DOID:0050902	OMIM:155255	J:102702

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c⁺ Trp53^tm1Tyj/Trp53⁺
Genetic Background	involves: 129S1/Sv * 129S2/SvPas * C57BL/6

Find Mice

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

neoplasm

increased medulloblastoma incidence ( J:102702 )

• small increase in tumor incidence (2/20) after irradiation at P5 or 6 with 4 Gy radiation

nervous system

increased medulloblastoma incidence ( J:102702 )

• small increase in tumor incidence (2/20) after irradiation at P5 or 6 with 4 Gy radiation

Allelic Composition	Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd Ptch1^tm1Mps/Ptch1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

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

neoplasm

increased medulloblastoma incidence ( J:205254 )

• 7 of 11 mutants exhibit invasive medulloblastoma

nervous system

increased medulloblastoma incidence ( J:205254 )

• 7 of 11 mutants exhibit invasive medulloblastoma

abnormal cerebellar molecular layer ( J:205254 )

• 1 month old cerebella show preneoplastic lesions in the outer molecular layer where progenitors within the external germinal layer previously resided, suggesting that medulloblastomas arise from granule neuron progenitors

Allelic Composition	Cdkn2b^tm1Bbd/Cdkn2b^tm1Bbd Cdkn2c^tm1Bbd/Cdkn2c^tm1Bbd
Genetic Background	involves: 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2b^tm1Bbd mutation (1 available); any Cdkn2b mutation (7 available)
Cdkn2c^tm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)

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

neoplasm

increased tumor incidence ( J:63299 )

increased pituitary adenoma incidence ( J:63299 )

increased testis tumor incidence ( J:63299 )

• testicular (Leydig cell) tumors

increased lymphoma incidence ( J:63299 )

increased sarcoma incidence ( J:63299 )

• angiosarcomas appear in aged mice

endocrine/exocrine glands

abnormal mammary gland morphology ( J:63299 )

• cysts in mammary glands

pancreas cyst ( J:63299 )

abnormal testis morphology ( J:63299 )

• cysts in the testis

dilated rete testis ( J:63299 )

• seen in 37.5% of males

seminiferous tubule degeneration ( J:63299 )

• 37.5% of males show atrophy of the seminiferous tubes

enlarged testis ( J:63299 )

• 37.5% of males show enlarged testes with severe dilatation of the tubules of the rete testis with atrophy of seminiferous tubes, similar to human testicular dysplasia

increased pituitary adenoma incidence ( J:63299 )

increased testis tumor incidence ( J:63299 )

• testicular (Leydig cell) tumors

hematopoietic system

enlarged spleen ( J:63299 )

extramedullary hematopoiesis ( J:63299 )

abnormal Langerhans cell morphology ( J:63299 )

• Langerhans islet hyperplasia

abnormal lymphocyte morphology ( J:63299 )

• lymphocytes show increased proliferation upon mitogenic stimulation

immune system

enlarged spleen ( J:63299 )

abnormal Langerhans cell morphology ( J:63299 )

• Langerhans islet hyperplasia

abnormal lymphocyte morphology ( J:63299 )

• lymphocytes show increased proliferation upon mitogenic stimulation

lymph node hyperplasia ( J:63299 )

lymphoid hyperplasia ( J:63299 )

• 55% of mutants develop lymphoproliferative disorders to a similar extent as single Cdkn2b homozygotes

renal/urinary system

kidney cyst ( J:63299 )

reproductive system

abnormal testis morphology ( J:63299 )

• cysts in the testis

dilated rete testis ( J:63299 )

• seen in 37.5% of males

seminiferous tubule degeneration ( J:63299 )

• 37.5% of males show atrophy of the seminiferous tubes

enlarged testis ( J:63299 )

• 37.5% of males show enlarged testes with severe dilatation of the tubules of the rete testis with atrophy of seminiferous tubes, similar to human testicular dysplasia

increased testis tumor incidence ( J:63299 )

• testicular (Leydig cell) tumors

cellular

abnormal cell physiology ( J:63299 )

• MEFs are susceptible to oncogenic ras transformation

increased fibroblast proliferation ( J:63299 )

• MEFs exhibit a higher proliferation rate and plating efficiency than wild-type MEFs, similar to single Cdkn2b homozygotes

integument

abnormal mammary gland morphology ( J:63299 )

• cysts in mammary glands

nervous system

increased pituitary adenoma incidence ( J:63299 )

growth/size/body

pancreas cyst ( J:63299 )

kidney cyst ( J:63299 )

enlarged spleen ( J:63299 )

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