Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse Generation ?+F1 (27-NOV-07)   Donating Investigator Colleen Croniger,   Case Western Reserve University

Description
Significant numbers of mice homozygous for this C/EBP-beta mutationon this mixed genetic background die perinatally due to hypoglycemia and a failure to mobilize glycogen. Homozygous males that survive to adulthood are fertile, but females are sterile, and display altered mammary duct formation. Macrophages isolated from homozygous mutant mice have impaired bactericidal activity. Surviving homozygotes exhibit fasting hypoglycemia, with reduced plasma insulin, plasma lipids, and free fatty acids (FFAs), and impaired hepatic glucose production. Further, they have a blunted response to glucagon and adrenaline primarily due to altered levels of hepatic cAMP production and reduced protein kinase A activity. Homozygous mice are resistant to obesity and have increased carbon dioxide production from increased metabolism in the brown adipose tissue and muscle. On a high-fat diet, homozygotes are protected from obesity and fatty liver due to reduced hepatic expression of lipogenic genes. Homozygotes may also exhibit a hematopoietic/lymphoproliferative disorder resembling Castleman's disease in humans. These C/EBP-beta mutant mice may be useful in studying metabolism, obesity, mammary gland development, or lymphoproliferative disorders.

Development
A targeting vector was used to replace the carboxy-terminal 72 amino acids of the protein which codes for the leucine zipper and part of the basic domain, with an MCI-Neo poly(A)+ cassette. This construct was electroporated into 129S/SvEv-Gpi1^c-derived CCE embryonic stem (ES) cells, and correctly targeted ES cells were microinjected into C57BL/6 blastocysts. Male chimeras were mated to outbred MF1 females to obtain heterozygous offspring. Heterozygous mice were bred together to generate homozygous mice on this mixed 129S and MF1 genetic background.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cebpb^tm1Vpo/Cebpb^tm1Vpo

        involves: 129S/SvEv * MF1

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:25215)
  • only 12% of homozygotes, instead of the expected Mendelian ratio of 25%, are obtained at weaning, indicating postnatal lethality
• life span-post-weaning/aging
• premature death (MGI Ref ID J:25215)
  • homozygotes raised in a non-specific pathogen-free facility display an additional 50% increase in mortality during the first few weeks post-weaning
• hematopoietic system phenotype
• abnormal hematopoiesis (MGI Ref ID J:25215)
• abnormal plasma cell morphology (MGI Ref ID J:25215)
  • in addition to extensive plasmacytosis in the spleen and lymph nodes, homozygotes show significant infiltration of plasma cells in the peribronchial region of the lung, kidney stroma, and in portal areas of the liver
• extramedullary hematopoiesis (MGI Ref ID J:25215)
  • homozygotes exhibit extramedullary hematopoiesis in the spleen, lymph nodes (partial penetrance) and liver (not shown)
  • 6 of 20 homozygotes contain lymph nodes with myelocytes present at varying stages of maturation, suggesting deregulated hematopoietic proliferation
• abnormal spleen red pulp morphology (MGI Ref ID J:25215)
  • homozygotes display a hyperplastic red pulp, with many aggregates of plasma cells intermixed with hematopoietic tissue containing numerous megakaryocytes and mature granulocytes
  • in severely enlarged spleens, the red pulp is engulfed by erythroid cells
• abnormal spleen white pulp morphology (MGI Ref ID J:25215)
  • homozygotes display a hyperplastic white pulp relative to wild-type mice
• abnormal spleen secondary B follicle morphology (MGI Ref ID J:25215)
  • homozygotes exhibit large lymphoid follicles with wide germinal centers in the white pulp
  • homozygotes develop an age-related expansion of the B-cell compartment in the spleen, as shown by abnormally high numbers of B220⁺ cells
• enlarged spleen (MGI Ref ID J:25215)
  • starting at 16 weeks of age, homozygotes exhibit splenomegaly
• increased bone marrow cell number (MGI Ref ID J:25215)
  • homozygotes show bone marrow hyperplasia with a prevalence of myeloblasts, mature granulocytes and megakaryocytes
• homeostasis/metabolism phenotype
• abnormal enzyme/ coenzyme level (MGI Ref ID J:52286)
  • adult fed female homozygotes show a 42% reduction in adipose tissue cAMP levels relative to wild-type mice; in addition, both basal and glucagon-stimulated hepatic cAMP levels are significantly reduced
• abnormal glucose homeostasis (MGI Ref ID J:52286)
  • after an 18-hr overnight fast, adult female homozygotes exhibit an ~40% reduction in basal hepatic glucose production (HGP) relative to wild-type mice
  • during a pancreatic clamp, overnight-fasted female homozygotes show glucagon resistance, failing to exhibit a significant increase in HGP in response to glucagon infusion; in contrast, wild-type mice respond to glucagon stimulation by a ~38% increase in HGP
  • at 16-20 weeks, homozygotes exhibit a significant increase in whole-body insulin-stimulated glucose disposal along with accelerated glucose metabolism in skeletal muscle
• abnormal gluconeogenesis (MGI Ref ID J:52286)
  • adult female homozygotes exhibit reduced gluconeogenesis during fasting
• decreased circulating insulin level (MGI Ref ID J:62132)
  • after a 6-hr fast, adult homozygotes exhibit a 35% reduction in plasma insulin levels relative to wild-type mice
• hypoglycemia (MGI Ref ID J:52286)
  • in the fed state, adult female homozygotes exhibit normal plasma glucose levels relative to wild-type mice
  • after a 6-hr fast, adult homozygotes exhibit a 25% reduction in plasma glucose levels relative to wild-type mice
  • after an 18-hr overnight fast, female homozygotes exhibit hypoglycemia, with plasma glucose levels ~30% lower than wild-type levels while insulin levels remain relatively normal
  • fasting hypoglycemia is associated with normal levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase gene expression, despite a reduction in net liver glycogenolysis
• increased insulin sensitivity (MGI Ref ID J:62132)
  • adult homozygotes exhibit increased whole-body insulin sensitivity, probably as a result of reduced plasma FFA levels and enhanced insulin signaling in skeletal muscle
  • increased insulin-stimulated glucose disposal is primarily due to an increase in glucose uptake in peripheral tissues rather than enhanced suppression of HGP by insulin
  • in contrast to enhanced insulin action in skeletal muscle, adult homozygotes exhibit a normal metabolic and gene regulatory response to insulin in liver and adipose tissue
• reduced glycogen catabolism rate (MGI Ref ID J:52286)
  • at the end of pancreatic clamp, adult female homozygotes show a 22% reduction in net hepatic glycogen depletion, suggesting a defect in hepatic glycogen mobilization in response to fasting and glucagon infusion
• abnormal lipid homeostasis (MGI Ref ID J:62132)
  • after an 18-hr overnight fast, adult female homozygotes show a 40% increase in the amount of DNA per gram of adipose tissue, suggesting reduced lipid content per cell
• abnormal circulating free fatty acids level (MGI Ref ID J:52286)
  • in response to epinephrine, adult fed homozygotes show a 68% reduction in FFA release from periovarian fat-pads relative to wild-type mice, indicating impaired lipolysis
  • notably, Bt2 cAMP, augments FFA release 2-fold above epinephrine-stimulated FFA levels in mutant females, compared with no additional change in wild-type mice
• decreased circulating free fatty acid level (MGI Ref ID J:52286)
  • at the end of a pancreatic clamp, overnight-fasted adult homozygotes show a 50% reduction in FFA and 3-hydroxybutyrate levels relative to wild-type mice; a 43% decrease in plasma lactate levels is also observed
  • adult homozygotes show reduced fasting plasma FFA levels before a hyperinsulinemic clamp and during the first 100 min of insulin infusion; after 100 min of hyperinsulinemia, mutant and wild-type mice show a comparable level of suppression of plasma FFA
• decreased circulating triglyceride level (MGI Ref ID J:52286)
  • after an 18-hr overnight fast, adult female homozygotes show a 31% reduction in circulating triglyceride levels relative to wild-type mice
• impaired lipolysis (MGI Ref ID J:62132)
  • impaired lipolysis i.e. FFA release from mutant periovarian fat-pads is most likely due to inability to generate cAMP in response to epinephrine
• decreased circulating leptin level (MGI Ref ID J:62132)
  • at 16-20 weeks, reduced adipose tissue mass is associated with significantly reduced plasma leptin levels
• hemosiderosis (MGI Ref ID J:25215)
  • homozygotes exhibit hemosiderosis in the red pulp of the spleen
• increased circulating corticosterone level (MGI Ref ID J:52286)
  • after an 18-hr overnight fast, adult female homozygotes exhibit a slight increase in circulating corticosterone levels relative to wild-type mice
• increased circulating interleukin-6 level (MGI Ref ID J:25215)
  • nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age
• muscle phenotype
• abnormal muscle cell glucose uptake (MGI Ref ID J:62132)
  • in vitro, skeletal muscles from homozygotes show increased insulin-stimulated glucose transport activity and elevated IRS-1 protein levels
• immune system phenotype
• abnormal axillary lymph node morphology (MGI Ref ID J:25215)
  • homozygotes exhibit enlarged lacrimal and peribronchial lymph nodes relative to wild-type mice
• abnormal cell-mediated immunity (MGI Ref ID J:25215)
• abnormal T-helper 1 physiology (MGI Ref ID J:25215)
  • in response to systemic candidiasis, homozygotes exhibit an impaired Th1-type response and a strong Th2-type response, in accord with a reactive lymphoproliferative disorder
• abnormal T-helper 2 physiology (MGI Ref ID J:25215)
  • in response to systemic candidiasis, homozygotes develop a non-protective Th2-biased response, as shown by elevated levels of Candida-specific antibodies of the IgG1 rather than the IgG2a isotype
  • Th2 cytokines IL-4 and IL-6 are increasingly produced by CD4⁺ cells in Candida-susceptible homozygotes, while progressively disappearing in resistant wild-type mice
• abnormal macrophage physiology (MGI Ref ID J:25215)
  • upon in vitro activation with IFN-gamma plus LPS, splenic macrophages obtained from mutant mice fail to release nitric oxide, either before or after C. albicans infection
  • notably, mutant splenic macrophages display significantly reduced candidacidal activity relative to wild-type macrophages
• increased IgG level (MGI Ref ID J:25215)
  • ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice
• abnormal humoral immune response (MGI Ref ID J:25215)
• increased IgG level (MGI Ref ID J:25215)
  • ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice
• abnormal inguinal lymph node morphology (MGI Ref ID J:25215)
  • homozygotes exhibit enlarged inguinal lymph nodes relative to wild-type mice
• abnormal innate immunity (MGI Ref ID J:25215)
• abnormal macrophage physiology (MGI Ref ID J:25215)
  • upon in vitro activation with IFN-gamma plus LPS, splenic macrophages obtained from mutant mice fail to release nitric oxide, either before or after C. albicans infection
  • notably, mutant splenic macrophages display significantly reduced candidacidal activity relative to wild-type macrophages
• abnormal interleukin physiology (MGI Ref ID J:25215)
  • in response to systemic candidiasis, homozygotes fail to exhibit a significant increase in serum IL-12 levels, indicating an impaired Th1 response
• abnormal lymph node cortex (MGI Ref ID J:25215)
• abnormal lymph node B cell domain (MGI Ref ID J:25215)
• abnormal lymph node secondary follicle (MGI Ref ID J:25215)
  • homozygotes have hyperplastic lymphoid follicles and enlarged germinal centers containing lymphocytes in varying stages of "blast" transformation in the cortex
  • homozygotes develop an age-related expansion of the B-cell compartment in the lymph nodes, as shown by abnormally high numbers of B220⁺ cells
• abnormal lymph node T cell domain (MGI Ref ID J:25215)
  • homozygotes contain numerous sheets and aggregates of mostly mature plasma cells in the compressed paracortical region of hyperplastic lymph nodes
• abnormal lymph node medulla (MGI Ref ID J:25215)
  • homozygotes exhibit an enlarged medulla, with medullary cords packed with sheets and aggregates of mostly mature plasma cells in pseudotumoral arrangement
• abnormal mesenteric lymph node morphology (MGI Ref ID J:25215)
  • homozygotes exhibit enlarged mesenteric lymph nodes relative to wild-type mice
• abnormal mucosa-associated lymphoid tissue morphology (MGI Ref ID J:25215)
  • starting at 16 weeks of age, homozygotes exhibit mucosal swelling
• abnormal plasma cell morphology (MGI Ref ID J:25215)
  • in addition to extensive plasmacytosis in the spleen and lymph nodes, homozygotes show significant infiltration of plasma cells in the peribronchial region of the lung, kidney stroma, and in portal areas of the liver
• abnormal spleen red pulp morphology (MGI Ref ID J:25215)
  • homozygotes display a hyperplastic red pulp, with many aggregates of plasma cells intermixed with hematopoietic tissue containing numerous megakaryocytes and mature granulocytes
  • in severely enlarged spleens, the red pulp is engulfed by erythroid cells
• abnormal spleen white pulp morphology (MGI Ref ID J:25215)
  • homozygotes display a hyperplastic white pulp relative to wild-type mice
• abnormal spleen secondary B follicle morphology (MGI Ref ID J:25215)
  • homozygotes exhibit large lymphoid follicles with wide germinal centers in the white pulp
  • homozygotes develop an age-related expansion of the B-cell compartment in the spleen, as shown by abnormally high numbers of B220⁺ cells
• decreased susceptibility to type IV hypersensitivity reaction (MGI Ref ID J:25215)
  • in response to systemic candidiasis, homozygotes show impaired DTH reactivity (measured as footpad weight increase) at 10 days after PCA-2 infection, indicating an impaired Th1-type response
• enlarged lymph nodes (MGI Ref ID J:25215)
  • starting at 16 weeks of age, homozygotes display enlarged peripheral lymph nodes (lymphoadenopathy)
• enlarged submandibular lymph nodes (MGI Ref ID J:25215)
• enlarged spleen (MGI Ref ID J:25215)
  • starting at 16 weeks of age, homozygotes exhibit splenomegaly
• glomerulonephritis (MGI Ref ID J:25215)
• increased circulating interleukin-6 level (MGI Ref ID J:25215)
  • nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age
• increased susceptibility to fungal infection (MGI Ref ID J:25215)
  • homozygotes are more susceptible to a low inoculum (i.v., 10⁵ cells) of the CA-6 strain of C. albicans, with ~88% homozygotes dying within 14 days while all wild-type mice survive
  • both wild-type and mutant mice survive challenge with 10⁶ cells of the low virulence PCA-2 strain; however, unlike wild-type mice, homozygotes fail to survive a subsequent lethal CA-6 challenge, with a high number of C. albicans cells found in the kidney
  • increased susceptibility to C. albicans infection is associated with predominance of a Th2-type response
• renal/urinary system phenotype
• abnormal renal glomerulus morphology (MGI Ref ID J:25215)
  • 7 of 20 homozygotes show enlarged glomeruli
• abnormal mesangial cell (MGI Ref ID J:25215)
  • 7 of 20 homozygotes exhibit an increase in mesangial cells and mesangial matrix
• glomerulonephritis (MGI Ref ID J:25215)
• skin/coat/nails phenotype
• skin lesions (MGI Ref ID J:25215)
  • homozygotes raised under SPF conditions develop skin lesions with increasing age
  • skin lesions are more frequent and severe and appear earlier in homozygotes exposed to pathogens
• adipose tissue phenotype
• abnormal adipose tissue physiology (MGI Ref ID J:52286)
  • adult fed female homozygotes show a 42% reduction in adipose tissue cAMP levels relative to wild-type mice
  • impaired lipolysis i.e. FFA release from mutant periovarian fat-pads is most likely due to inability to generate cAMP in response to epinephrine
• abnormal fat pad morphology (MGI Ref ID J:52286)
  • after an 18-hr overnight fast, adult female homozygotes exhibit an ~50% reduction in the weight of periuterine fat-pad relative to wild-type mice
• abnormal gonadal fat pad morphology (MGI Ref ID J:62132)
  • at 16-20 weeks, adult homozygotes show a ~38% reduction in gonadal fat pad weight relative to wild-type mice
• decreased percent body fat (MGI Ref ID J:62132)
  • at 16-20 weeks, homozygotes show a 38% reduction in total body lipid content relative to wild-type mice; however, the average body weight is not significantly altered

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cebpb^tm1Vpo/Cebpb⁺

        involves: 129S/SvEv * C57BL/6 * MF1

• endocrine/exocrine gland phenotype
• abnormal mammary gland morphology (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), ~20% of virgin female heterozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds
  • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of the ductal epithelium
  • transplantation of heterozygous mammary epithelium into cleared mammary fat pads of nude mice results in an intermediate phenotype consisting of both normal and bloated ducts
• reproductive system phenotype
• abnormal mammary gland morphology (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), ~20% of virgin female heterozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds
  • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of the ductal epithelium
  • transplantation of heterozygous mammary epithelium into cleared mammary fat pads of nude mice results in an intermediate phenotype consisting of both normal and bloated ducts

Cebpb^tm1Vpo/Cebpb^tm1Vpo

        involves: 129S/SvEv * C57BL/6 * MF1

• endocrine/exocrine gland phenotype
• abnormal mammary gland morphology (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), all virgin female homozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds; no morphological differences are noted at 5 weeks
  • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells
  • transplantation of mutant mammary epithelium into cleared mammary fat pads of nude mice results in primarily bloated ducts, localizing the ductal defect to the mammary epithelium
• abnormal mammary gland development (MGI Ref ID J:48513)
  • all virgin female homozygotes exhibit abnormal mammary ductal development
  • following simulation of pregnancy by E+P treatment, homozygotes exhibit varying degrees of impairment of lobuloalveolar development, with large areas of ductal epithelium lacking secondary/tertiary side branches or alveoli; a small % of homozygotes show complete absence of alveolar development
• abnormal branching of the mammary ductal tree (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching
  • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes
• abnormal mammary gland physiology (MGI Ref ID J:48513)
  • when cultured on Matrigel, primary mammary epithelial cells from E+P-treated homozygotes fail to functionally differentiate in response to lactogenic hormones: WAP expression is undetectable while expression of beta-casein is inhibited by 85%-100%
• reproductive system phenotype
• abnormal mammary gland morphology (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), all virgin female homozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds; no morphological differences are noted at 5 weeks
  • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells
  • transplantation of mutant mammary epithelium into cleared mammary fat pads of nude mice results in primarily bloated ducts, localizing the ductal defect to the mammary epithelium
• abnormal mammary gland development (MGI Ref ID J:48513)
  • all virgin female homozygotes exhibit abnormal mammary ductal development
  • following simulation of pregnancy by E+P treatment, homozygotes exhibit varying degrees of impairment of lobuloalveolar development, with large areas of ductal epithelium lacking secondary/tertiary side branches or alveoli; a small % of homozygotes show complete absence of alveolar development
• abnormal branching of the mammary ductal tree (MGI Ref ID J:48513)
  • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching
  • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes
• abnormal mammary gland physiology (MGI Ref ID J:48513)
  • when cultured on Matrigel, primary mammary epithelial cells from E+P-treated homozygotes fail to functionally differentiate in response to lactogenic hormones: WAP expression is undetectable while expression of beta-casein is inhibited by 85%-100%
• female infertility (MGI Ref ID J:48513)
  • female homozygotes are sterile
• homeostasis/metabolism phenotype
• abnormal glucose homeostasis (MGI Ref ID J:49673)
• abnormal gluconeogenesis (MGI Ref ID J:49673)
  • after partial hepatectomy, homozygotes show abnormal expression of a subset of genes involved in hepatocyte gluconeogenesis
• hypoglycemia (MGI Ref ID J:49673)
  • unlike hepatectomized wild-type mice, homozygotes fail to exhibit normalization of serum glucose levels at 36-40 hrs and sustain their hypoglycemic state until 48 hrs posthepatectomy
  • in contrast, serum cholesterol and triglyceride levels show no significant differences posthepatectomy
• liver/biliary system phenotype
• decreased liver regeneration (MGI Ref ID J:49673)
  • following two-thirds hepatectomy, homozygotes display impaired liver regeneration, with hepatocyte DNA synthesis reduced to 25-30% of wild-type levels at 40 hrs after surgery
  • no significant differences in the rate of liver mass reconstitution are observed, suggesting that increased cellular size may be independent of DNA synthesis
  • decreased liver regeneration is associated with prolonged hypoglycemia at 36-40 hrs posthepatectomy and dysregulation of several genes involved in hepatocyte gluconeogenesis and growth regulation

Cebpb^tm1Vpo/Cebpb^tm1Vpo

        FVB.129S-Cebpb^tm1Vpo

• cellular phenotype
• decreased apoptosis (MGI Ref ID J:52729)
  • MEFs exhibit delayed onset of cell death and detachment from the plate after challenge with tunicamycin, an ER stressor, compared to controls

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Other (altered fat metabolism)
Other (altered lipoprotein profile)

Developmental Biology Research
Internal/Organ Defects (hematopoietic defects)
Lymphoid Tissue Defects (hematopoietic defects)
Perinatal Lethality (Homozygous)

Diabetes and Obesity Research
Hypoglycemia
Hypoinsulinemia
Impaired Insulin Processing

Endocrine Deficiency Research
Mammary Gland Defects

Hematological Research
Hematopoietic Defects

Immunology and Inflammation Research
Lymphoid Tissue Defects (hematopoietic development)

Metabolism Research
Lipid Metabolism

Reproductive Biology Research
Fertility Defects (females only)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cebpbtm1Vpo
Allele Name		targeted mutation 1, Valeria Poli
Allele Type		Targeted (knock-out)
Common Name(s)		C/EBPb-; C/EBPbeta-; Cebpb-;
Mutation Made By		Valeria Poli,   University of Dundee
Strain of Origin		129S/SvEv-Gpi1
ES Cell Line Name		CCE/EK.CCE
ES Cell Line Strain		129S/SvEv-Gpi1
Gene Symbol and Name		Cebpb, CCAAT/enhancer binding protein (C/EBP), beta
Chromosome		2
Gene Common Name(s)		C/EBP BETA; C/EBP-beta; C/EBPbeta; CRP2; IL-6DBP; IL6DBP; LAP; MGC32080; NF-IL6; NF-M; Nfil6; TCF5; nuclear protein Il6;
General Note		Mice homozygous for this targeted mutation exhibit a pathology that is almost identical to multicentric Castleman's disease in human patients, characterized by splenomegaly, peripheral lymphoadenopathy, enhanced hematopoiesis, and deregulated IL-6 production (J:25215).
Molecular Note		An MC1-neocassette replaced the carboxy-terminal part of the gene, which encodes the leucine zipper and part of the basic domain. Generation of a null allele was confirmed by Northern blots of hepatic tissue. [MGI Ref ID J:52286]

Genotyping

Genotyping Information

Genotyping Protocols

Cebpb^tm1Vpo, HRM, vers. 2
Cebpb^tm1Vpo, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Klose J. 1999. Genotypes and phenotypes. Electrophoresis 20(4-5):643-52. [PubMed: 10344229]  [MGI Ref ID J:55286]

Millward CA; Heaney JD; Sinasac DS; Chu EC; Bederman IR; Gilge DA; Previs SF; Croniger CM. 2007. Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta are protected against diet-induced obesity. Diabetes 56(1):161-7. [PubMed: 17192478]  [MGI Ref ID J:121694]

Screpanti I; Romani L; Musiani P; Modesti A; Fattori E; Lazzaro D; Sellitto C; Scarpa S; Bellavia D; Lattanzio G; Bistoni F; Frati L; Cortese R; Gulino A; Ciliberto G; Costantini F; Poli V. 1995. Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice [published erratum appears in EMBO J 1995 Jul 17;14(14):3596] EMBO J 14(9):1932-41. [PubMed: 7744000]  [MGI Ref ID J:25215]

Additional References

Cebpb^tm1Vpo related

Buck M; Chojkier M. 2007. A Ribosomal S-6 Kinase-Mediated Signal to C/EBP-beta Is Critical for the Development of Liver Fibrosis. PLoS ONE 2(12):e1372. [PubMed: 18159255]  [MGI Ref ID J:131072]

Buck M; Chojkier M. 2007. C/EBPbeta phosphorylation rescues macrophage dysfunction and apoptosis induced by anthrax lethal toxin. Am J Physiol Cell Physiol 293(6):C1788-96. [PubMed: 17855774]  [MGI Ref ID J:128753]

Buck M; Poli V; van der Geer P; Chojkier M; Hunter T. 1999. Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha. Mol Cell 4(6):1087-92. [PubMed: 10635333]  [MGI Ref ID J:133506]

Carmona MC; Hondares E; Rodriguez de la Concepcion ML; Rodriguez-Sureda V; Peinado-Onsurbe J; Poli V; Iglesias R; Villarroya F; Giralt M. 2005. Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPbeta. Biochem J 389(Pt 1):47-56. [PubMed: 15762841]  [MGI Ref ID J:117502]

Cortes-Canteli M; Luna-Medina R; Sanz-Sancristobal M; Alvarez-Barrientos A; Santos A; Perez-Castillo A. 2008. CCAAT/enhancer binding protein beta deficiency provides cerebral protection following excitotoxic injury. J Cell Sci 121(Pt 8):1224-34. [PubMed: 18388310]  [MGI Ref ID J:139594]

Croniger C; Trus M; Lysek-Stupp K; Cohen H; Liu Y; Darlington GJ; Poli V; Hanson RW; Reshef L. 1997. Role of the isoforms of CCAAT/enhancer-binding protein in the initiation of phosphoenolpyruvate carboxykinase (GTP) gene transcription at birth. J Biol Chem 272(42):26306-12. [PubMed: 9334201]  [MGI Ref ID J:101974]

Croniger CM; Millward C; Yang J; Kawai Y; Arinze IJ; Liu S; Harada-Shiba M; Chakravarty K; Friedman JE; Poli V; Hanson RW. 2001. Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta have an attenuated response to cAMP and impaired carbohydrate metabolism. J Biol Chem 276(1):629-38. [PubMed: 11024029]  [MGI Ref ID J:66828]

Dodig M; Ogunwale B; Dasarathy S; Li M; Wang B; McCullough AJ. 2007. Differences in regulation of type I collagen synthesis in primary and passaged hepatic stellate cell cultures: the role of alpha5beta1-integrin. Am J Physiol Gastrointest Liver Physiol 293(1):G154-64. [PubMed: 17510195]  [MGI Ref ID J:123625]

Greenbaum LE; Li W; Cressman DE; Peng Y; Ciliberto G; Poli V; Taub R. 1998. CCAAT enhancer- binding protein beta is required for normal hepatocyte proliferation in mice after partial hepatectomy. J Clin Invest 102(5):996-1007. [PubMed: 9727068]  [MGI Ref ID J:49673]

Grimm SL; Contreras A; Barcellos-Hoff MH; Rosen JM. 2005. Cell cycle defects contribute to a block in hormone-induced mammary gland proliferation in CCAAT/enhancer-binding protein (C/EBPbeta)-null mice. J Biol Chem 280(43):36301-9. [PubMed: 16120603]  [MGI Ref ID J:102696]

Grimm SL; Seagroves TN; Kabotyanski EB; Hovey RC; Vonderhaar BK; Lydon JP; Miyoshi K; Hennighausen L; Ormandy CJ; Lee AV; Stull MA; Wood TL; Rosen JM. 2002. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol 16(12):2675-91. [PubMed: 12456789]  [MGI Ref ID J:125450]

Hirai H; Zhang P; Dayaram T; Hetherington CJ; Mizuno S; Imanishi J; Akashi K; Tenen DG. 2006. C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol 7(7):732-9. [PubMed: 16751774]  [MGI Ref ID J:112664]

Liu S; Croniger C; Arizmendi C; Harada-Shiba M; Ren J; Poli V; Hanson RW; Friedman JE. 1999. Hypoglycemia and impaired hepatic glucose production in mice with a deletion of the C/EBPbeta gene. J Clin Invest 103(2):207-13. [PubMed: 9916132]  [MGI Ref ID J:52286]

Maytin EV; Lin JC; Krishnamurthy R; Batchvarova N; Ron D; Mitchell PJ; Habener JF. 1999. Keratin 10 gene expression during differentiation of mouse epidermis requires transcription factors C/EBP and AP-2. Dev Biol 216(1):164-81. [PubMed: 10588870]  [MGI Ref ID J:58864]

Schroeder-Gloeckler JM; Rahman SM; Janssen RC; Qiao L; Shao J; Roper M; Fischer SJ; Lowe E; Orlicky DJ; McManaman JL; Palmer C; Gitomer WL; Huang W; O'Doherty RM; Becker TC; Klemm DJ; Jensen DR; Pulawa LK; Eckel RH; Friedman JE. 2007. CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice. J Biol Chem 282(21):15717-29. [PubMed: 17387171]  [MGI Ref ID J:122719]

Screpanti I; Musiani P; Bellavia D; Cappelletti M; Aiello FB; Maroder M; Frati L; Modesti A; Gulino A; Poli V. 1996. Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice. J Exp Med 184(4):1561-6. [PubMed: 8879230]  [MGI Ref ID J:35883]

Seagroves TN; Krnacik S; Raught B; Gay J; Burgess-Beusse B; Darlington GJ; Rosen JM. 1998. C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes Dev 12(12):1917-28. [PubMed: 9637692]  [MGI Ref ID J:48513]

Seagroves TN; Lydon JP; Hovey RC; Vonderhaar BK; Rosen JM. 2000. C/EBPbeta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development. Mol Endocrinol 14(3):359-68. [PubMed: 10707954]  [MGI Ref ID J:60761]

Stephanou A; Conroy S; Isenberg DA; Maione D; Poli V; Ciliberto G; Latchman DS. 1998. Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (hsp90) and the production of anti-hsp90 antibodies. J Autoimmun 11(3):249-53. [PubMed: 9693973]  [MGI Ref ID J:48553]

Timchenko NA; Wilde M; Darlington GJ. 1999. C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Mol Cell Biol 19(4):2936-45. [PubMed: 10082561]  [MGI Ref ID J:53930]

Wang H; Larris B; Peiris TH; Zhang L; Le Lay J; Gao Y; Greenbaum LE. 2007. C/EBPbeta activates E2F-regulated genes in vivo via recruitment of the coactivator CREB-binding protein/P300. J Biol Chem 282(34):24679-88. [PubMed: 17599912]  [MGI Ref ID J:124659]

Wang L; Shao J; Muhlenkamp P; Liu S; Klepcyk P; Ren J; Friedman JE. 2000. Increased insulin receptor substrate-1 and enhanced skeletal muscle insulin sensitivity in mice lacking CCAAT/enhancer-binding protein beta. J Biol Chem 275(19):14173-81. [PubMed: 10747954]  [MGI Ref ID J:62132]

Zinszner H; Kuroda M; Wang X; Batchvarova N; Lightfoot RT; Remotti H; Stevens JL; Ron D. 1998. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12(7):982-95. [PubMed: 9531536]  [MGI Ref ID J:52729]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice are bred together or to wildtype siblings. The donating investigator reports increased penetrance of perinatal lethality when backcrossed to C57BL/6 genetic background.
Mating System	+/+ sibling x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.