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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Cdkn2btm1Bbd
targeted mutation 1, Mariano Barbacid
MGI:1933760
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
 		Cdkn2btm1Bbd/Cdkn2btm1Bbd involves: 129S1/Sv * C57BL/6 MGI:2175772
cn2
 		Cdkn2btm1Bbd/Cdkn2btm1Bbd
Pbx1tm1Koss/Pbx1tm1Koss
Nkx2-5tm2(cre)Rph/Nkx2-5+ 		involves: 129P2/OlaHsd * 129S1/Sv MGI:5426986
cx3
 		Cdkn2btm1Bbd/Cdkn2btm1Bbd
Cdkn2ctm1Bbd/Cdkn2ctm1Bbd 		involves: 129S1/Sv * C57BL/6 MGI:2662500


Genotype
MGI:2175772
hm1
Allelic
Composition		 Cdkn2btm1Bbd/Cdkn2btm1Bbd
Genetic
Background		 involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2btm1Bbd mutation (1 available); any Cdkn2b mutation (7 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
mortality/aging
premature death ( J:63299 )
• some mice die between 9 and 18 months of age; these mice have no evidence of tumors but have severe extramedullary hematopoiesis

immune system
abnormal lymphocyte morphology ( J:63299 )
• lymphocytes exhibit increased proliferation upon mitogenic stimulation
increased mature B cell number ( J:63299 )
• increase in levels of mature B cells in spleen and lymph nodes
abnormal spleen marginal zone morphology ( J:63299 )
• enlarged marginal zones
abnormal lymph node secondary follicle morphology ( J:63299 )
• reactive lymph nodes characterized by prominent secondary follicles
abnormal lymph node germinal center morphology ( J:63299 )
• enlarged germinal centers
lymphoid hyperplasia ( J:63299 )
• mutants exhibit lymphoproliferative disorders

neoplasm
increased tumor incidence ( J:63299 )
• 8.2% incidence of tumors
• however, mutants do not show increased incidence of chemically-induced tumors
increased adenocarcinoma incidence ( J:63299 )
• adenocarcinomas of the lung and pancreas
increased sarcoma incidence ( J:63299 )
• 73% of tumors are of connective tissue origin, including angiosarcomas and skin fibrosarcoma

hematopoietic system
extramedullary hematopoiesis ( J:63299 )
• in the spleen
abnormal lymphocyte morphology ( J:63299 )
• lymphocytes exhibit increased proliferation upon mitogenic stimulation
increased mature B cell number ( J:63299 )
• increase in levels of mature B cells in spleen and lymph nodes
abnormal spleen marginal zone morphology ( J:63299 )
• enlarged marginal zones

cellular
abnormal cell physiology ( J:63299 )
• MEFs are susceptible to ras oncogenic transformation
increased fibroblast proliferation ( J:63299 )
• MEFs exhibit a higher proliferation rate and plating efficiency than wild-type MEFs
• serum starved MEFs re-enter the cell cycle more efficiently than wild-type MEFs

growth/size/body
spleen hyperplasia ( J:63299 )




Genotype
MGI:5426986
cn2
Allelic
Composition		 Cdkn2btm1Bbd/Cdkn2btm1Bbd
Pbx1tm1Koss/Pbx1tm1Koss
Nkx2-5tm2(cre)Rph/Nkx2-5+
Genetic
Background		 involves: 129P2/OlaHsd * 129S1/Sv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2btm1Bbd mutation (1 available); any Cdkn2b mutation (7 available)
Nkx2-5tm2(cre)Rph mutation (1 available); any Nkx2-5 mutation (21 available)
Pbx1tm1Koss mutation (0 available); any Pbx1 mutation (40 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal spleen morphology ( J:184521 )
• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage
abnormal spleen mesenchyme morphology ( J:184521 )
• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b

immune system
abnormal spleen morphology ( J:184521 )
• partial rescue of spleen expansion compared to mutant mice wild-type for Cdkn2b and spleens form a single compact anlage
abnormal spleen mesenchyme morphology ( J:184521 )
• significant rescue of mesenchymal proliferation compared to mutant mice wild-type for Cdkn2b




Genotype
MGI:2662500
cx3
Allelic
Composition		 Cdkn2btm1Bbd/Cdkn2btm1Bbd
Cdkn2ctm1Bbd/Cdkn2ctm1Bbd
Genetic
Background		 involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2btm1Bbd mutation (1 available); any Cdkn2b mutation (7 available)
Cdkn2ctm1Bbd mutation (1 available); any Cdkn2c mutation (16 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased testis tumor incidence ( J:63299 )
• testicular (Leydig cell) tumors
increased sarcoma incidence ( J:63299 )
• angiosarcomas appear in aged mice

endocrine/exocrine glands
abnormal mammary gland morphology ( J:63299 )
• cysts in mammary glands
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

hematopoietic system
abnormal Langerhans cell morphology ( J:63299 )
• Langerhans islet hyperplasia
abnormal lymphocyte morphology ( J:63299 )
• lymphocytes show increased proliferation upon mitogenic stimulation

immune system
abnormal Langerhans cell morphology ( J:63299 )
• Langerhans islet hyperplasia
abnormal lymphocyte morphology ( J:63299 )
• lymphocytes show increased proliferation upon mitogenic stimulation
lymphoid hyperplasia ( J:63299 )
• 55% of mutants develop lymphoproliferative disorders to a similar extent as single Cdkn2b homozygotes

renal/urinary system

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

growth/size/body
pancreas cyst ( J:63299 )
kidney cyst ( J:63299 )
enlarged spleen ( J:63299 )




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04/23/2024
MGI 6.23 		The Jackson Laboratory