B6.Cg-Ikbkb^tm2Cgn/Cnrm

Status	Available to order
EMMA ID	EM:01921
International strain name	B6.Cg-Ikbkb^tm2Cgn/Cnrm
Alternative name	IKK2FL (IKK2floxed)
Strain type	Targeted Mutant Strains : Conditional mutation
Allele/Transgene symbol	Ikbkb^tm2Cgn,
Gene/Transgene symbol	Ikbkb

Information from provider

Provider	Klaus Rajewsky
Provider affiliation	CBR Institute for Biomedical Research, Immune Disease Institute
Genetic information	The Ikbkb (IKK2) targeting vector was constructed by placing a 2kb EcoRI-BglII genomic fragment, containing exons 6 and 7, between the loxP-flanked PGKneo cassette and the third loxP site. An upstream 2.6 kb ScaI-EcoRI fragment and a 4.2 kb downstream BglII fragment were used as arms for homology. Bruce 4 ES cells derived from B6 mice were cultured, transfected and selected as previously described. Homologous recombinant clones were isolated and the loxP flanked PGKneo cassette was excised by transient expression of cre recombinase. Germ-line transmitting chimeras were generated using ES cells carrying the floxed Ikbkb gene.
Phenotypic information	Upon cre recombinase-mediated deletion of exons 6 and 7, which correspond to nucleotides 389-567 of the coding Ikbkb (IKK2) cDNA sequence, premature termination codons are introduced, thus producing an Ikbkb null allele.
References	FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses.;Victoratos Panayiotis, Lagnel Jacques, Tzima Sotiria, Alimzhanov Marat B, Rajewsky Klaus, Pasparakis Manolis, Kollias George, ;2006;Immunity;24;65-77; 16413924 TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2.;Pasparakis Manolis, Courtois Gilles, Hafner Martin, Schmidt-Supprian Marc, Nenci Arianna, Toksoy Atiye, Krampert Monika, Goebeler Matthias, Gillitzer Reinhard, Israel Alain, Krieg Thomas, Rajewsky Klaus, Haase Ingo, ;2002;Nature;417;861-6; 12075355 IkappaB kinase signaling is essential for maintenance of mature B cells.;Pasparakis Manolis, Schmidt-Supprian Marc, Rajewsky Klaus, ;2002;The Journal of experimental medicine;196;743-52; 12235208 Mature T cells depend on signaling through the IKK complex.;Schmidt-Supprian Marc, Courtois Gilles, Tian Jane, Coyle Anthony J, Israël Alain, Rajewsky Klaus, Pasparakis Manolis, ;2003;Immunity;19;377-89; 14499113 Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice.;Kanters Edwin, Pasparakis Manolis, Gijbels Marion J J, Vergouwe Monique N, Partouns-Hendriks Iris, Fijneman Remond J A, Clausen Björn E, Förster Irmgard, Kockx Mark M, Rajewsky Klaus, Kraal Georg, Hofker Marten H, de Winther Menno P J, ;2003;The Journal of clinical investigation;112;1176-85; 14561702 Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation.;Schmidt-Supprian Marc, Tian Jane, Grant Ethan P, Pasparakis Manolis, Maehr René, Ovaa Huib, Ploegh Hidde L, Coyle Anthony J, Rajewsky Klaus, ;2004;Proceedings of the National Academy of Sciences of the United States of America;101;4566-71; 15070758 I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell help, germinal center reactions, and homeostatic expansion.;Schmidt-Supprian Marc, Tian Jane, Ji Hongbin, Terhorst Cox, Bhan Atul K, Grant Ethan P, Pasparakis Manolis, Casola Stefano, Coyle Anthony J, Rajewsky Klaus, ;2004;Journal of immunology (Baltimore, Md. : 1950);173;1612-9; 15265889 Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury.;Luedde Tom, Assmus Ulrike, Wüstefeld Torsten, Meyer zu Vilsendorf Andreas, Roskams Tania, Schmidt-Supprian Mark, Rajewsky Klaus, Brenner David A, Manns Michael P, Pasparakis Manolis, Trautwein Christian, ;2005;The Journal of clinical investigation;115;849-59; 15776110 IKK mediates ischemia-induced neuronal death.;Herrmann Oliver, Baumann Bernd, de Lorenzi Rossana, Muhammad Sajjad, Zhang Wen, Kleesiek Jens, Malfertheiner Max, Köhrmann Martin, Potrovita Ioana, Maegele Ira, Beyer Cordian, Burke James R, Hasan Mazahir T, Bujard Hermann, Wirth Thomas, Pasparakis Manolis, Schwaninger Markus, ;2005;Nature medicine;11;1322-9; 16286924 Localized inflammatory skin disease following inducible ablation of I kappa B kinase 2 in murine epidermis.;Stratis Athanasios, Pasparakis Manolis, Markur Doreen, Knaup Renate, Pofahl Ruth, Metzger Daniel, Chambon Pierre, Krieg Thomas, Haase Ingo, ;2006;The Journal of investigative dermatology;126;614-20; 16397523

Information from EMMA

Archiving centre	CNR, Consiglio Nazionale delle Ricerche, Monterotondo, Italy

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

Severe combined immunodeficiency due to IKK2 deficiency / Orphanet_397787

Literature references

FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses.;Victoratos Panayiotis, Lagnel Jacques, Tzima Sotiria, Alimzhanov Marat B, Rajewsky Klaus, Pasparakis Manolis, Kollias George, ;2006;Immunity;24;65-77; 16413924
TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2.;Pasparakis Manolis, Courtois Gilles, Hafner Martin, Schmidt-Supprian Marc, Nenci Arianna, Toksoy Atiye, Krampert Monika, Goebeler Matthias, Gillitzer Reinhard, Israel Alain, Krieg Thomas, Rajewsky Klaus, Haase Ingo, ;2002;Nature;417;861-6; 12075355
IkappaB kinase signaling is essential for maintenance of mature B cells.;Pasparakis Manolis, Schmidt-Supprian Marc, Rajewsky Klaus, ;2002;The Journal of experimental medicine;196;743-52; 12235208
Mature T cells depend on signaling through the IKK complex.;Schmidt-Supprian Marc, Courtois Gilles, Tian Jane, Coyle Anthony J, Israël Alain, Rajewsky Klaus, Pasparakis Manolis, ;2003;Immunity;19;377-89; 14499113
Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice.;Kanters Edwin, Pasparakis Manolis, Gijbels Marion J J, Vergouwe Monique N, Partouns-Hendriks Iris, Fijneman Remond J A, Clausen Björn E, Förster Irmgard, Kockx Mark M, Rajewsky Klaus, Kraal Georg, Hofker Marten H, de Winther Menno P J, ;2003;The Journal of clinical investigation;112;1176-85; 14561702
Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-kappaB activation.;Schmidt-Supprian Marc, Tian Jane, Grant Ethan P, Pasparakis Manolis, Maehr René, Ovaa Huib, Ploegh Hidde L, Coyle Anthony J, Rajewsky Klaus, ;2004;Proceedings of the National Academy of Sciences of the United States of America;101;4566-71; 15070758
I kappa B kinase 2 deficiency in T cells leads to defects in priming, B cell help, germinal center reactions, and homeostatic expansion.;Schmidt-Supprian Marc, Tian Jane, Ji Hongbin, Terhorst Cox, Bhan Atul K, Grant Ethan P, Pasparakis Manolis, Casola Stefano, Coyle Anthony J, Rajewsky Klaus, ;2004;Journal of immunology (Baltimore, Md. : 1950);173;1612-9; 15265889
Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury.;Luedde Tom, Assmus Ulrike, Wüstefeld Torsten, Meyer zu Vilsendorf Andreas, Roskams Tania, Schmidt-Supprian Mark, Rajewsky Klaus, Brenner David A, Manns Michael P, Pasparakis Manolis, Trautwein Christian, ;2005;The Journal of clinical investigation;115;849-59; 15776110
IKK mediates ischemia-induced neuronal death.;Herrmann Oliver, Baumann Bernd, de Lorenzi Rossana, Muhammad Sajjad, Zhang Wen, Kleesiek Jens, Malfertheiner Max, Köhrmann Martin, Potrovita Ioana, Maegele Ira, Beyer Cordian, Burke James R, Hasan Mazahir T, Bujard Hermann, Wirth Thomas, Pasparakis Manolis, Schwaninger Markus, ;2005;Nature medicine;11;1322-9; 16286924
Localized inflammatory skin disease following inducible ablation of I kappa B kinase 2 in murine epidermis.;Stratis Athanasios, Pasparakis Manolis, Markur Doreen, Knaup Renate, Pofahl Ruth, Metzger Daniel, Chambon Pierre, Krieg Thomas, Haase Ingo, ;2006;The Journal of investigative dermatology;126;614-20; 16397523

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Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740^*
Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740^*
Rederivation of mice from frozen stock, delivery time available upon request . €3880^*

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Genotyping protocol

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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.Cg-Ikbkbtm2Cgn/Cnrm