129-Raf1^tm2Bacc/Biat

Status	Available to order
EMMA ID	EM:15079
International strain name	129-Raf1^tm2Bacc/Biat
Alternative name	129Sv cRaf F/F
Strain type	Targeted Mutant Strains : Conditional mutation
Allele/Transgene symbol	Raf1^tm2Bacc,
Gene/Transgene symbol	Raf1

Information from provider

Provider	Manuela Baccarini
Provider affiliation	Department of Microbiology, Immunobiology & Genetics, University
Genetic information	A targeting vector containing loxP sites 5′ and 3′ of exon 3 was designed. A third loxP site as well as selection markers (a neomycin resistance gene for positive selection and the HSV thymidine kinase gene for negative selection) were inserted upstream of the floxed exon 3. The mutation was introduced into E14.1 embryonic stem cells by homologous recombination, and the Neo/TK gene cassette was then deleted by transiently expressing cre recombinase. See Jesenberger V, et al. Protective role of Raf-1 in Salmonella-induced macrophage apoptosis, J Exp Med. 2001, Feb 5;193(3):353-64
Phenotypic information	Homozygous: c-Raf-1 (f/f) mice are phenotypically normal and fertile. When bred to mice expressing the cre recombinase under the control of a tissue-specific promoter, exon 3 of c-Raf-1 is deleted, which leads to the complete loss of the Raf-1 protein in the tissue of interest. Heterozygous: Mice are phenotypically normal and fertile.
Breeding history	Backcrossed to 129/Sv background for more than 10 generations.
References	c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.;Blasco Rafael B, Francoz Sarah, Santamaría David, Cañamero Marta, Dubus Pierre, Charron Jean, Baccarini Manuela, Barbacid Mariano, ;2011;Cancer cell;19;652-63; 21514245 TNFR1 promotes tumor necrosis factor-mediated mouse colon epithelial cell survival through RAF activation of NF-kappaB.;Edelblum Karen L, Goettel Jeremy A, Koyama Tatsuki, McElroy Steven J, Yan Fang, Polk D Brent, ;2008;The Journal of biological chemistry;283;29485-94; 18713739 Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription.;Alejandro Emilyn U, Lim Gareth E, Mehran Arya E, Hu Xiaoke, Taghizadeh Farnaz, Pelipeychenko Dmytro, Baccarini Manuela, Johnson James D, ;2011;FASEB journal : official publication of the Federation of American Societies for Experimental Biology;25;3884-95; 21817126 Skin tumorigenesis stimulated by Raf inhibitors relies upon Raf functions that are dependent and independent of ERK.;Doma Eszter, Rupp Christian, Varga Andrea, Kern Florian, Riegler Bettina, Baccarini Manuela, ;2013;Cancer research;73;6926-37; 24129679 Essential role of B-Raf in ERK activation during extraembryonic development.;Galabova-Kovacs Gergana, Matzen Dana, Piazzolla Daniela, Meissl Katrin, Plyushch Tatiana, Chen Adele P, Silva Alcino, Baccarini Manuela, ;2006;Proceedings of the National Academy of Sciences of the United States of America;103;1325-30; 16432225 Raf Kinases Are Essential for Phosphate Induction of ERK1/2 Phosphorylation in Hypertrophic Chondrocytes and Normal Endochondral Bone Development.;Papaioannou Garyfallia, Petit Elizabeth T, Liu Eva S, Baccarini Manuela, Pritchard Catrin, Demay Marie B, ;2017;The Journal of biological chemistry;292;3164-3171; 28073913 Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo.;Zhong Jian, Li Xiaoyan, McNamee Cara, Chen Adele P, Baccarini Manuela, Snider William D, ;2007;Nature neuroscience;10;598-607; 17396120 Protective role of Raf-1 in Salmonella-induced macrophage apoptosis.;Jesenberger V, Procyk K J, Rüth J, Schreiber M, Theussl H C, Wagner E F, Baccarini M, ;2001;The Journal of experimental medicine;193;353-64; 11157055 Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor.;Mathew Grinu, Hannan Abdul, Hertzler-Schaefer Kristina, Wang Fen, Feng Gen-Sheng, Zhong Jian, Zhao Jean J, Downward Julian, Zhang Xin, ;2016;Proceedings of the National Academy of Sciences of the United States of America;113;13156-13161; 27799550 B-Raf and C-Raf are required for melanocyte stem cell self-maintenance.;Valluet Agathe, Druillennec Sabine, Barbotin Céline, Dorard Coralie, Monsoro-Burq Anne H, Larcher Magalie, Pouponnot Celio, Baccarini Manuela, Larue Lionel, Eychène Alain, ;2012;Cell reports;2;774-80; 23022482 Raf-1 addiction in Ras-induced skin carcinogenesis.;Ehrenreiter Karin, Kern Florian, Velamoor Vanishree, Meissl Katrin, Galabova-Kovacs Gergana, Sibilia Maria, Baccarini Manuela, ;2009;Cancer cell;16;149-60; 19647225 A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis.;Jeric Ines, Maurer Gabriele, Cavallo Anna Lina, Raguz Josipa, Desideri Enrico, Tarkowski Bartosz, Parrini Matthias, Fischer Irmgard, Zatloukal Kurt, Baccarini Manuela, ;2016;Nature communications;7;13781; 28000790 Epidermal RAF prevents allergic skin disease.;Raguz Josipa, Jeric Ines, Niault Theodora, Nowacka Joanna Daniela, Kuzet Sanya Eduarda, Rupp Christian, Fischer Irmgard, Biggi Silvia, Borsello Tiziana, Baccarini Manuela, ;2016;eLife;5;217-228.e4; 27431613 c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling.;Sanclemente Manuel, Francoz Sarah, Esteban-Burgos Laura, Bousquet-Mur Emilie, Djurec Magdolna, Lopez-Casas Pedro P, Hidalgo Manuel, Guerra Carmen, Drosten Matthias, Musteanu Monica, Barbacid Mariano, ;2018;Cancer cell;33;406-20; 29395869 Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer.;Eser Stefan, Reiff Nina, Messer Marlena, Seidler Barbara, Gottschalk Kathleen, Dobler Melanie, Hieber Maren, Arbeiter Andreas, Klein Sabine, Kong Bo, Michalski Christoph W, Schlitter Anna Melissa, Esposito Irene, Kind Alexander J, Rad Lena, Schnieke Angelika E, Baccarini Manuela, Alessi Dario R, Rad Roland, Schmid Roland M, Schneider Günter, Saur Dieter, ;2013;Cancer cell;23;937-43; 23453624 Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis.;Yamaguchi Osamu, Watanabe Tetsuya, Nishida Kazuhiko, Kashiwase Kazunori, Higuchi Yoshiharu, Takeda Toshihiro, Hikoso Shungo, Hirotani Shinichi, Asahi Michio, Taniike Masayuki, Nakai Atsuko, Tsujimoto Ikuko, Matsumura Yasushi, Miyazaki Jun-ichi, Chien Kenneth R, Matsuzawa Atsushi, Sadamitsu Chiharu, Ichijo Hidenori, Baccarini Manuela, Hori Masatsugu, Otsu Kinya, ;2004;The Journal of clinical investigation;114;573-587.e6; 15467832 Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.;Blasco María Teresa, Navas Carolina, Martín-Serrano Guillermo, Graña-Castro Osvaldo, Lechuga Carmen G, Martín-Díaz Laura, Djurec Magdolna, Li Jing, Morales-Cacho Lucia, Esteban-Burgos Laura, Perales-Patón Javier, Bousquet-Mur Emilie, Castellano Eva, Jacob Harrys K C, Cabras Lavinia, Musteanu Monica, Drosten Matthias, Ortega Sagrario, Mulero Francisca, Sainz Bruno, Dusetti Nelson, Iovanna Juan, Sánchez-Bueno Francisco, Hidalgo Manuel, Khiabanian Hossein, Rabadán Raul, Al-Shahrour Fátima, Guerra Carmen, Barbacid Mariano, ;2019;Cancer cell;35;348-55; 30975481 c-Raf promotes angiogenesis during normal growth plate maturation.;Liu Eva S, Raimann Adalbert, Chae Byongsoo Timothy, Martins Janaina S, Baccarini Manuela, Demay Marie B, ;2016;Development (Cambridge, England);143;955-64; 26657770 Raf-1 regulates Rho signaling and cell migration.;Ehrenreiter Karin, Piazzolla Daniela, Velamoor Vanishree, Sobczak Izabela, Small J Victor, Takeda Junji, Leung Thomas, Baccarini Manuela, ;2005;The Journal of cell biology;168;2483-92; 15753127 Essential, non-redundant roles of B-Raf and Raf-1 in Ras-driven skin tumorigenesis.;Kern F, Doma E, Rupp C, Niault T, Baccarini M, ;2013;Oncogene;32;128-36; 22733131 C-Raf is required for the initiation of lung cancer by K-Ras(G12D).;Karreth Florian A, Frese Kristopher K, DeNicola Gina M, Baccarini Manuela, Tuveson David A, ;2011;Cancer discovery;1;; 22043453
Homozygous fertile	yes
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	University of Veterinary Medicine, Vienna, Austria
Animals used for archiving	heterozygous 129

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

Noonan syndrome / Orphanet_648
Noonan syndrome with multiple lentigines / Orphanet_500
Familial isolated dilated cardiomyopathy / Orphanet_154

Literature references

c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma.;Blasco Rafael B, Francoz Sarah, Santamaría David, Cañamero Marta, Dubus Pierre, Charron Jean, Baccarini Manuela, Barbacid Mariano, ;2011;Cancer cell;19;652-63; 21514245
TNFR1 promotes tumor necrosis factor-mediated mouse colon epithelial cell survival through RAF activation of NF-kappaB.;Edelblum Karen L, Goettel Jeremy A, Koyama Tatsuki, McElroy Steven J, Yan Fang, Polk D Brent, ;2008;The Journal of biological chemistry;283;29485-94; 18713739
Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription.;Alejandro Emilyn U, Lim Gareth E, Mehran Arya E, Hu Xiaoke, Taghizadeh Farnaz, Pelipeychenko Dmytro, Baccarini Manuela, Johnson James D, ;2011;FASEB journal : official publication of the Federation of American Societies for Experimental Biology;25;3884-95; 21817126
Skin tumorigenesis stimulated by Raf inhibitors relies upon Raf functions that are dependent and independent of ERK.;Doma Eszter, Rupp Christian, Varga Andrea, Kern Florian, Riegler Bettina, Baccarini Manuela, ;2013;Cancer research;73;6926-37; 24129679
Essential role of B-Raf in ERK activation during extraembryonic development.;Galabova-Kovacs Gergana, Matzen Dana, Piazzolla Daniela, Meissl Katrin, Plyushch Tatiana, Chen Adele P, Silva Alcino, Baccarini Manuela, ;2006;Proceedings of the National Academy of Sciences of the United States of America;103;1325-30; 16432225
Raf Kinases Are Essential for Phosphate Induction of ERK1/2 Phosphorylation in Hypertrophic Chondrocytes and Normal Endochondral Bone Development.;Papaioannou Garyfallia, Petit Elizabeth T, Liu Eva S, Baccarini Manuela, Pritchard Catrin, Demay Marie B, ;2017;The Journal of biological chemistry;292;3164-3171; 28073913
Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo.;Zhong Jian, Li Xiaoyan, McNamee Cara, Chen Adele P, Baccarini Manuela, Snider William D, ;2007;Nature neuroscience;10;598-607; 17396120
Protective role of Raf-1 in Salmonella-induced macrophage apoptosis.;Jesenberger V, Procyk K J, Rüth J, Schreiber M, Theussl H C, Wagner E F, Baccarini M, ;2001;The Journal of experimental medicine;193;353-64; 11157055
Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor.;Mathew Grinu, Hannan Abdul, Hertzler-Schaefer Kristina, Wang Fen, Feng Gen-Sheng, Zhong Jian, Zhao Jean J, Downward Julian, Zhang Xin, ;2016;Proceedings of the National Academy of Sciences of the United States of America;113;13156-13161; 27799550
B-Raf and C-Raf are required for melanocyte stem cell self-maintenance.;Valluet Agathe, Druillennec Sabine, Barbotin Céline, Dorard Coralie, Monsoro-Burq Anne H, Larcher Magalie, Pouponnot Celio, Baccarini Manuela, Larue Lionel, Eychène Alain, ;2012;Cell reports;2;774-80; 23022482
Raf-1 addiction in Ras-induced skin carcinogenesis.;Ehrenreiter Karin, Kern Florian, Velamoor Vanishree, Meissl Katrin, Galabova-Kovacs Gergana, Sibilia Maria, Baccarini Manuela, ;2009;Cancer cell;16;149-60; 19647225
A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis.;Jeric Ines, Maurer Gabriele, Cavallo Anna Lina, Raguz Josipa, Desideri Enrico, Tarkowski Bartosz, Parrini Matthias, Fischer Irmgard, Zatloukal Kurt, Baccarini Manuela, ;2016;Nature communications;7;13781; 28000790
Epidermal RAF prevents allergic skin disease.;Raguz Josipa, Jeric Ines, Niault Theodora, Nowacka Joanna Daniela, Kuzet Sanya Eduarda, Rupp Christian, Fischer Irmgard, Biggi Silvia, Borsello Tiziana, Baccarini Manuela, ;2016;eLife;5;217-228.e4; 27431613
c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling.;Sanclemente Manuel, Francoz Sarah, Esteban-Burgos Laura, Bousquet-Mur Emilie, Djurec Magdolna, Lopez-Casas Pedro P, Hidalgo Manuel, Guerra Carmen, Drosten Matthias, Musteanu Monica, Barbacid Mariano, ;2018;Cancer cell;33;406-20; 29395869
Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer.;Eser Stefan, Reiff Nina, Messer Marlena, Seidler Barbara, Gottschalk Kathleen, Dobler Melanie, Hieber Maren, Arbeiter Andreas, Klein Sabine, Kong Bo, Michalski Christoph W, Schlitter Anna Melissa, Esposito Irene, Kind Alexander J, Rad Lena, Schnieke Angelika E, Baccarini Manuela, Alessi Dario R, Rad Roland, Schmid Roland M, Schneider Günter, Saur Dieter, ;2013;Cancer cell;23;937-43; 23453624
Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis.;Yamaguchi Osamu, Watanabe Tetsuya, Nishida Kazuhiko, Kashiwase Kazunori, Higuchi Yoshiharu, Takeda Toshihiro, Hikoso Shungo, Hirotani Shinichi, Asahi Michio, Taniike Masayuki, Nakai Atsuko, Tsujimoto Ikuko, Matsumura Yasushi, Miyazaki Jun-ichi, Chien Kenneth R, Matsuzawa Atsushi, Sadamitsu Chiharu, Ichijo Hidenori, Baccarini Manuela, Hori Masatsugu, Otsu Kinya, ;2004;The Journal of clinical investigation;114;573-587.e6; 15467832
Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.;Blasco María Teresa, Navas Carolina, Martín-Serrano Guillermo, Graña-Castro Osvaldo, Lechuga Carmen G, Martín-Díaz Laura, Djurec Magdolna, Li Jing, Morales-Cacho Lucia, Esteban-Burgos Laura, Perales-Patón Javier, Bousquet-Mur Emilie, Castellano Eva, Jacob Harrys K C, Cabras Lavinia, Musteanu Monica, Drosten Matthias, Ortega Sagrario, Mulero Francisca, Sainz Bruno, Dusetti Nelson, Iovanna Juan, Sánchez-Bueno Francisco, Hidalgo Manuel, Khiabanian Hossein, Rabadán Raul, Al-Shahrour Fátima, Guerra Carmen, Barbacid Mariano, ;2019;Cancer cell;35;348-55; 30975481
c-Raf promotes angiogenesis during normal growth plate maturation.;Liu Eva S, Raimann Adalbert, Chae Byongsoo Timothy, Martins Janaina S, Baccarini Manuela, Demay Marie B, ;2016;Development (Cambridge, England);143;955-64; 26657770
Raf-1 regulates Rho signaling and cell migration.;Ehrenreiter Karin, Piazzolla Daniela, Velamoor Vanishree, Sobczak Izabela, Small J Victor, Takeda Junji, Leung Thomas, Baccarini Manuela, ;2005;The Journal of cell biology;168;2483-92; 15753127
Essential, non-redundant roles of B-Raf and Raf-1 in Ras-driven skin tumorigenesis.;Kern F, Doma E, Rupp C, Niault T, Baccarini M, ;2013;Oncogene;32;128-36; 22733131
C-Raf is required for the initiation of lung cancer by K-Ras(G12D).;Karreth Florian A, Frese Kristopher K, DeNicola Gina M, Baccarini Manuela, Tuveson David A, ;2011;Cancer discovery;1;; 22043453

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Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740^*
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129-Raf1tm2Bacc/Biat