B6.129-Cdkn2c^tm1Bbd/Cnbc

Status	Available to order
EMMA ID	EM:08027
Citation information	RRID:IMSR_EM:08027 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information.
International strain name	B6.129-Cdkn2c^tm1Bbd/Cnbc
Alternative name	Cdkn2c or p18Ink4c KO
Strain type	Targeted Mutant Strains : Knock-out
Allele/Transgene symbol	Cdkn2c^tm1Bbd
Gene/Transgene symbol	Cdkn2c

Information from provider

Provider	Mariano Barbacid
Provider affiliation	Molecular Oncology, Centro Nacional de Investigaciones Oncologicas
Genetic information	Exon 2, encoding amino acid residues 43-168, was replaced by a neomycin cassette. No protein was detected in Western blots of lysates derived from tissues of 3-month old homozygous mutant mice.
Phenotypic information	Homozygous: Mice lacking Cdkn2c (P18INK4c) have deregulated epithelial cell growth leading to the formation of cysts, mostly in the cortical region of the kidneys and the mammary epithelium. Loss of P18INK4c also leads to lymphoproliferative disorders. In addition to pituitary tumors, we have observed the appearance of tumors of testicular and adrenal gland (pheochromocytomas) origin in a significant fraction of P18INK4c (-/-) mice. Less frequently, these animals also develop tumors of lymphoid, connective and epithelial cell origin. Heterozygous: heterozygous mice are viable
Breeding history	Chimeras were bred with C57BL/6J females. Heterozygous mice were bred among themselves to generate homozygous mice or to C57BL/6J animals to propagate the targeted allele. Mice were bred for more than 10 generations with C57BL/6J mice before freezing.
References	Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis.;Latres E, Malumbres M, Sotillo R, Martín J, Ortega S, Martín-Caballero J, Flores J M, Cordón-Cardo C, Barbacid M, ;2000;The EMBO journal;19;3496-506; 10880462 Invasive melanoma in Cdk4-targeted mice.;Sotillo R, García J F, Ortega S, Martin J, Dubus P, Barbacid M, Malumbres M, ;2001;Proceedings of the National Academy of Sciences of the United States of America;98;13312-7; 11606789 Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity.;Sotillo Rocío, Renner Oliver, Dubus Pierre, Ruiz-Cabello Jesús, Martín-Caballero Juan, Barbacid Mariano, Carnero Amancio, Malumbres Marcos, ;2005;Cancer research;65;3846-52; 15867383 Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and p19(Ink4d).;Zindy F, den Besten W, Chen B, Rehg J E, Latres E, Barbacid M, Pollard J W, Sherr C J, Cohen P E, Roussel M F, ;2001;Molecular and cellular biology;21;3244-55; 11287627 Hemangiosarcomas, medulloblastomas, and other tumors in Ink4c/p53-null mice.;Zindy Frederique, Nilsson Lisa M, Nguyen Luc, Meunier Cecile, Smeyne Richard J, Rehg Jerold E, Eberhart Charles, Sherr Charles J, Roussel Martine F, ;2003;Cancer research;63;5420-7; 14500377 A molecular fingerprint for medulloblastoma.;Lee Youngsoo, Miller Heather L, Jensen Patricia, Hernan Roberto, Connelly Michele, Wetmore Cynthia, Zindy Frederique, Roussel Martine F, Curran Tom, Gilbertson Richard J, McKinnon Peter J, ;2003;Cancer research;63;5428-37; 14500378 The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation.;Uziel Tamar, Zindy Frederique, Xie Suqing, Lee Youngsoo, Forget Antoine, Magdaleno Susan, Rehg Jerold E, Calabrese Christopher, Solecki David, Eberhart Charles G, Sherr Sarah E, Plimmer Sarah, Clifford Steven C, Hatten Mary E, McKinnon Peter J, Gilbertson Richard J, Curran Tom, Sherr Charles J, Roussel Martine F, ;2005;Genes & development;19;2656-67; 16260494 N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development.;Zindy Frederique, Knoepfler Paul S, Xie Suqing, Sherr Charles J, Eisenman Robert N, Roussel Martine F, ;2006;Proceedings of the National Academy of Sciences of the United States of America;103;11579-83; 16864777 Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis.;Nilsson L M, Keller U B, Yang C, Nilsson J A, Cleveland J L, Roussel M F, ;2007;Oncogene;26;2833-9; 17099725 Genetic alterations in mouse medulloblastomas and generation of tumors de novo from primary cerebellar granule neuron precursors.;Zindy Frederique, Uziel Tamar, Ayrault Olivier, Calabrese Christopher, Valentine Marc, Rehg Jerold E, Gilbertson Richard J, Sherr Charles J, Roussel Martine F, ;2007;Cancer research;67;2676-84; 17363588
Homozygous fertile	yes
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	CNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain
Animals used for archiving	heterozygous C57BL/6J males, wild-type C57BL/6J females
Stage of embryos	2-cell

Disease and phenotype information

MGI phenotypes (allele matching)

kidney cortex cysts / MGI
cortical renal glomerulopathies / MGI
mammary gland hyperplasia / MGI
pituitary gland hyperplasia / MGI
lymphoid hyperplasia / MGI
enlarged spleen / MGI
enlarged lymph nodes / MGI
abnormal cerebellar molecular layer / MGI
enlarged testis / MGI
Leydig cell hyperplasia / MGI
increased body weight / MGI
increased body size / MGI
abnormal apoptosis / MGI
neoplasm / MGI
increased B cell derived lymphoma incidence / MGI
increased T cell derived lymphoma incidence / MGI
increased pituitary adenoma incidence / MGI
increased pheochromocytoma incidence / MGI
premature death / MGI
abnormal lymph node medulla morphology / MGI
decreased circulating testosterone level / MGI
increased hemangiosarcoma incidence / MGI
kidney cysts / MGI
abnormal neuronal migration / MGI
increased testis tumor incidence / MGI
increased spleen white pulp amount / MGI
abnormal mammary gland epithelium morphology / MGI
abnormal neuron differentiation / MGI
increased renal carcinoma incidence / MGI
abnormal Leydig cell differentiation / MGI

MGI phenotypes (gene matching)

increased bone marrow cell number / MGI
kidney cortex cysts / MGI
cortical renal glomerulopathies / MGI
abnormal mammary gland morphology / MGI
mammary gland hyperplasia / MGI
pituitary gland hyperplasia / MGI
enlarged pituitary gland / MGI
enlarged adrenal glands / MGI
lymphoid hyperplasia / MGI
enlarged spleen / MGI
spleen hyperplasia / MGI
enlarged lymph nodes / MGI
thymus hyperplasia / MGI
abnormal cerebellar molecular layer / MGI
small testis / MGI
enlarged testis / MGI
Leydig cell hyperplasia / MGI
increased body weight / MGI
weight loss / MGI
increased body size / MGI
ataxia / MGI
dehydration / MGI
abnormal apoptosis / MGI
neoplasm / MGI
increased B cell derived lymphoma incidence / MGI
increased T cell derived lymphoma incidence / MGI
increased lung adenocarcinoma incidence / MGI
increased pituitary adenoma incidence / MGI
increased lung adenoma incidence / MGI
increased pheochromocytoma incidence / MGI
premature death / MGI
abnormal lymph node medulla morphology / MGI
abnormal thymus size / MGI
abnormal T cell physiology / MGI
decreased circulating testosterone level / MGI
increased hemangiosarcoma incidence / MGI
kidney cysts / MGI
increased B cell number / MGI
increased T cell number / MGI
abnormal neuronal migration / MGI
increased testis tumor incidence / MGI
increased lung tumor incidence / MGI
abnormal pituitary intermediate lobe morphology / MGI
increased spleen white pulp amount / MGI
abnormal mammary gland epithelium morphology / MGI
abnormal neuron differentiation / MGI
increased mammary gland tumor incidence / MGI
increased renal carcinoma incidence / MGI
increased bronchioalveolar stem cell number / MGI
abnormal Leydig cell differentiation / MGI

Literature references

Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in proliferation and tumorigenesis.;Latres E, Malumbres M, Sotillo R, Martín J, Ortega S, Martín-Caballero J, Flores J M, Cordón-Cardo C, Barbacid M, ;2000;The EMBO journal;19;3496-506; 10880462
Invasive melanoma in Cdk4-targeted mice.;Sotillo R, García J F, Ortega S, Martin J, Dubus P, Barbacid M, Malumbres M, ;2001;Proceedings of the National Academy of Sciences of the United States of America;98;13312-7; 11606789
Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity.;Sotillo Rocío, Renner Oliver, Dubus Pierre, Ruiz-Cabello Jesús, Martín-Caballero Juan, Barbacid Mariano, Carnero Amancio, Malumbres Marcos, ;2005;Cancer research;65;3846-52; 15867383
Control of spermatogenesis in mice by the cyclin D-dependent kinase inhibitors p18(Ink4c) and p19(Ink4d).;Zindy F, den Besten W, Chen B, Rehg J E, Latres E, Barbacid M, Pollard J W, Sherr C J, Cohen P E, Roussel M F, ;2001;Molecular and cellular biology;21;3244-55; 11287627
Hemangiosarcomas, medulloblastomas, and other tumors in Ink4c/p53-null mice.;Zindy Frederique, Nilsson Lisa M, Nguyen Luc, Meunier Cecile, Smeyne Richard J, Rehg Jerold E, Eberhart Charles, Sherr Charles J, Roussel Martine F, ;2003;Cancer research;63;5420-7; 14500377
A molecular fingerprint for medulloblastoma.;Lee Youngsoo, Miller Heather L, Jensen Patricia, Hernan Roberto, Connelly Michele, Wetmore Cynthia, Zindy Frederique, Roussel Martine F, Curran Tom, Gilbertson Richard J, McKinnon Peter J, ;2003;Cancer research;63;5428-37; 14500378
The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation.;Uziel Tamar, Zindy Frederique, Xie Suqing, Lee Youngsoo, Forget Antoine, Magdaleno Susan, Rehg Jerold E, Calabrese Christopher, Solecki David, Eberhart Charles G, Sherr Sarah E, Plimmer Sarah, Clifford Steven C, Hatten Mary E, McKinnon Peter J, Gilbertson Richard J, Curran Tom, Sherr Charles J, Roussel Martine F, ;2005;Genes & development;19;2656-67; 16260494
N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development.;Zindy Frederique, Knoepfler Paul S, Xie Suqing, Sherr Charles J, Eisenman Robert N, Roussel Martine F, ;2006;Proceedings of the National Academy of Sciences of the United States of America;103;11579-83; 16864777
Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis.;Nilsson L M, Keller U B, Yang C, Nilsson J A, Cleveland J L, Roussel M F, ;2007;Oncogene;26;2833-9; 17099725
Genetic alterations in mouse medulloblastomas and generation of tumors de novo from primary cerebellar granule neuron precursors.;Zindy Frederique, Uziel Tamar, Ayrault Olivier, Calabrese Christopher, Valentine Marc, Rehg Jerold E, Gilbertson Richard J, Sherr Charles J, Roussel Martine F, ;2007;Cancer research;67;2676-84; 17363588

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Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740^*

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Practical information

Genotyping protocol

Example health report
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Material Transfer Agreement (MTA)
Distribution of this strain is subject to a provider MTA. Both signing of the MTA and submission of the online EMMA Mutant Request Form are required before material can be shipped.

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B6.129-Cdkn2ctm1Bbd/Cnbc