Strain Name:

STOCK Cebpbtm1Vpo/J

Stock Number:

006873

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These CCAAT/enhancer binding protein (C/EBP), beta knock-out mutant mice may be useful in studying metabolism, obesity, mammary gland development, or lymphoproliferative disorders.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
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Mating System+/+ sibling x Heterozygote         (Female x Male)   28-NOV-07
Specieslaboratory mouse
Generation?+F16 (28-OCT-13)
Generation Definitions
 
Donating Investigator Colleen Croniger,   Case Western Reserve University

Description
Significant numbers of mice homozygous for this C/EBP-beta mutation on 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-Gpi1c-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 provided by MGI
      assigned by genotype

Cebpbtm1Vpo/Cebpbtm1Vpo

        involves: 129S/SvEv * MF1
  • mortality/aging
  • partial postnatal lethality
    • only 12% of homozygotes, instead of the expected Mendelian ratio of 25%, are obtained at weaning, indicating postnatal lethality   (MGI Ref ID J:25215)
  • premature death
    • homozygotes raised in a non-specific pathogen-free facility display an additional 50% increase in mortality during the first few weeks post-weaning   (MGI Ref ID J:25215)
  • hematopoietic system phenotype
  • abnormal T-helper 1 physiology
    • 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   (MGI Ref ID J:25215)
  • abnormal T-helper 2 physiology
    • 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   (MGI Ref ID J:25215)
    • 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   (MGI Ref ID J:25215)
  • abnormal hematopoiesis   (MGI Ref ID J:25215)
    • abnormal plasma cell morphology
      • 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   (MGI Ref ID J:25215)
    • extramedullary hematopoiesis
      • homozygotes exhibit extramedullary hematopoiesis in the spleen, lymph nodes (partial penetrance) and liver (not shown)   (MGI Ref ID J:25215)
      • 6 of 20 homozygotes contain lymph nodes with myelocytes present at varying stages of maturation, suggesting deregulated hematopoietic proliferation   (MGI Ref ID J:25215)
  • abnormal macrophage physiology
    • 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   (MGI Ref ID J:25215)
    • notably, mutant splenic macrophages display significantly reduced candidacidal activity relative to wild-type macrophages   (MGI Ref ID J:25215)
  • abnormal spleen red pulp morphology
    • homozygotes display a hyperplastic red pulp, with many aggregates of plasma cells intermixed with hematopoietic tissue containing numerous megakaryocytes and mature granulocytes   (MGI Ref ID J:25215)
    • in severely enlarged spleens, the red pulp is engulfed by erythroid cells   (MGI Ref ID J:25215)
  • abnormal spleen white pulp morphology
    • homozygotes display a hyperplastic white pulp relative to wild-type mice   (MGI Ref ID J:25215)
    • abnormal spleen secondary B follicle morphology
      • homozygotes exhibit large lymphoid follicles with wide germinal centers in the white pulp   (MGI Ref ID J:25215)
      • homozygotes develop an age-related expansion of the B-cell compartment in the spleen, as shown by abnormally high numbers of B220+ cells   (MGI Ref ID J:25215)
  • enlarged spleen
    • starting at 16 weeks of age, homozygotes exhibit splenomegaly   (MGI Ref ID J:25215)
  • increased IgG level
    • ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice   (MGI Ref ID J:25215)
  • increased bone marrow cell number
    • homozygotes show bone marrow hyperplasia with a prevalence of myeloblasts, mature granulocytes and megakaryocytes   (MGI Ref ID J:25215)
  • homeostasis/metabolism phenotype
  • abnormal enzyme/ coenzyme level
    • 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   (MGI Ref ID J:52286)
  • abnormal glucose homeostasis
    • after an 18-hr overnight fast, adult female homozygotes exhibit an ~40% reduction in basal hepatic glucose production (HGP) relative to wild-type mice   (MGI Ref ID J:52286)
    • 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   (MGI Ref ID J:52286)
    • at 16-20 weeks, homozygotes exhibit a significant increase in whole-body insulin-stimulated glucose disposal along with accelerated glucose metabolism in skeletal muscle   (MGI Ref ID J:62132)
    • abnormal gluconeogenesis
      • adult female homozygotes exhibit reduced gluconeogenesis during fasting   (MGI Ref ID J:52286)
    • decreased circulating insulin level
      • after a 6-hr fast, adult homozygotes exhibit a 35% reduction in plasma insulin levels relative to wild-type mice   (MGI Ref ID J:62132)
    • decreased glycogen catabolism rate
      • 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   (MGI Ref ID J:52286)
    • hypoglycemia
      • in the fed state, adult female homozygotes exhibit normal plasma glucose levels relative to wild-type mice   (MGI Ref ID J:52286)
      • after a 6-hr fast, adult homozygotes exhibit a 25% reduction in plasma glucose levels relative to wild-type mice   (MGI Ref ID J:62132)
      • 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   (MGI Ref ID J:52286)
      • fasting hypoglycemia is associated with normal levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase gene expression, despite a reduction in net liver glycogenolysis   (MGI Ref ID J:52286)
    • increased insulin sensitivity
      • adult homozygotes exhibit increased whole-body insulin sensitivity, probably as a result of reduced plasma FFA levels and enhanced insulin signaling in skeletal muscle   (MGI Ref ID J:62132)
      • 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   (MGI Ref ID J:62132)
      • 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   (MGI Ref ID J:62132)
  • 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   (MGI Ref ID J:52286)
    • abnormal circulating free fatty acids level
      • 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   (MGI Ref ID J:52286)
      • 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   (MGI Ref ID J:52286)
      • decreased circulating free fatty acid level
        • 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   (MGI Ref ID J:52286)
        • 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   (MGI Ref ID J:62132)
    • decreased circulating triglyceride level
      • after an 18-hr overnight fast, adult female homozygotes show a 31% reduction in circulating triglyceride levels relative to wild-type mice   (MGI Ref ID J:52286)
    • impaired lipolysis
      • impaired lipolysis i.e. FFA release from mutant periovarian fat-pads is most likely due to inability to generate cAMP in response to epinephrine   (MGI Ref ID J:62132)
    • increased circulating corticosterone level
      • after an 18-hr overnight fast, adult female homozygotes exhibit a slight increase in circulating corticosterone levels relative to wild-type mice   (MGI Ref ID J:52286)
  • decreased circulating interleukin-12 level
    • in response to systemic candidiasis, homozygotes fail to exhibit a significant increase in serum IL-12 levels, indicating an impaired Th1 response   (MGI Ref ID J:25215)
  • decreased circulating leptin level
    • at 16-20 weeks, reduced adipose tissue mass is associated with significantly reduced plasma leptin levels   (MGI Ref ID J:62132)
  • hemosiderosis
    • homozygotes exhibit hemosiderosis in the red pulp of the spleen   (MGI Ref ID J:25215)
  • increased circulating interleukin-6 level
    • nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age   (MGI Ref ID J:25215)
  • muscle phenotype
  • abnormal muscle cell glucose uptake
    • in vitro, skeletal muscles from homozygotes show increased insulin-stimulated glucose transport activity and elevated IRS-1 protein levels   (MGI Ref ID J:62132)
  • immune system phenotype
  • abnormal cell-mediated immunity   (MGI Ref ID J:25215)
    • abnormal T-helper 1 physiology
      • 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   (MGI Ref ID J:25215)
    • abnormal T-helper 2 physiology
      • 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   (MGI Ref ID J:25215)
      • 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   (MGI Ref ID J:25215)
    • abnormal macrophage physiology
      • 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   (MGI Ref ID J:25215)
      • notably, mutant splenic macrophages display significantly reduced candidacidal activity relative to wild-type macrophages   (MGI Ref ID J:25215)
    • decreased susceptibility to type IV hypersensitivity reaction
      • 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   (MGI Ref ID J:25215)
    • increased IgG level
      • ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice   (MGI Ref ID J:25215)
  • abnormal humoral immune response   (MGI Ref ID J:25215)
    • increased IgG level
      • ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice   (MGI Ref ID J:25215)
  • abnormal innate immunity   (MGI Ref ID J:25215)
    • abnormal macrophage physiology
      • 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   (MGI Ref ID J:25215)
      • notably, mutant splenic macrophages display significantly reduced candidacidal activity relative to wild-type macrophages   (MGI Ref ID J:25215)
  • abnormal lymph node cortex morphology   (MGI Ref ID J:25215)
    • abnormal lymph node B cell domain morphology   (MGI Ref ID J:25215)
      • abnormal lymph node secondary follicle morphology
        • homozygotes have hyperplastic lymphoid follicles and enlarged germinal centers containing lymphocytes in varying stages of "blast" transformation in the cortex   (MGI Ref ID J:25215)
        • homozygotes develop an age-related expansion of the B-cell compartment in the lymph nodes, as shown by abnormally high numbers of B220+ cells   (MGI Ref ID J:25215)
    • abnormal lymph node T cell domain morphology
      • homozygotes contain numerous sheets and aggregates of mostly mature plasma cells in the compressed paracortical region of hyperplastic lymph nodes   (MGI Ref ID J:25215)
  • abnormal lymph node medulla morphology
    • homozygotes exhibit an enlarged medulla   (MGI Ref ID J:25215)
    • abnormal lymph node medullary cord morphology
      • homozygotes exhibit medullary cords packed with sheets and aggregates of mostly mature plasma cells in pseudotumoral arrangement   (MGI Ref ID J:25215)
  • abnormal mucosa-associated lymphoid tissue morphology
    • starting at 16 weeks of age, homozygotes exhibit mucosal swelling   (MGI Ref ID J:25215)
  • abnormal plasma cell morphology
    • 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   (MGI Ref ID J:25215)
  • abnormal spleen red pulp morphology
    • homozygotes display a hyperplastic red pulp, with many aggregates of plasma cells intermixed with hematopoietic tissue containing numerous megakaryocytes and mature granulocytes   (MGI Ref ID J:25215)
    • in severely enlarged spleens, the red pulp is engulfed by erythroid cells   (MGI Ref ID J:25215)
  • abnormal spleen white pulp morphology
    • homozygotes display a hyperplastic white pulp relative to wild-type mice   (MGI Ref ID J:25215)
    • abnormal spleen secondary B follicle morphology
      • homozygotes exhibit large lymphoid follicles with wide germinal centers in the white pulp   (MGI Ref ID J:25215)
      • homozygotes develop an age-related expansion of the B-cell compartment in the spleen, as shown by abnormally high numbers of B220+ cells   (MGI Ref ID J:25215)
  • decreased circulating interleukin-12 level
    • in response to systemic candidiasis, homozygotes fail to exhibit a significant increase in serum IL-12 levels, indicating an impaired Th1 response   (MGI Ref ID J:25215)
  • enlarged axillary lymph nodes
    • homozygotes exhibit enlarged lacrimal and peribronchial lymph nodes relative to wild-type mice   (MGI Ref ID J:25215)
  • enlarged inguinal lymph nodes
    • homozygotes exhibit enlarged inguinal lymph nodes relative to wild-type mice   (MGI Ref ID J:25215)
  • enlarged lymph nodes
    • starting at 16 weeks of age, homozygotes display enlarged peripheral lymph nodes (lymphoadenopathy)   (MGI Ref ID J:25215)
  • enlarged mesenteric lymph nodes
    • homozygotes exhibit enlarged mesenteric lymph nodes relative to wild-type mice   (MGI Ref ID J:25215)
  • enlarged spleen
    • starting at 16 weeks of age, homozygotes exhibit splenomegaly   (MGI Ref ID J:25215)
  • enlarged submandibular lymph nodes   (MGI Ref ID J:25215)
  • glomerulonephritis   (MGI Ref ID J:25215)
  • increased circulating interleukin-6 level
    • nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age   (MGI Ref ID J:25215)
  • increased susceptibility to fungal infection
    • 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   (MGI Ref ID J:25215)
    • 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   (MGI Ref ID J:25215)
    • increased susceptibility to C. albicans infection is associated with predominance of a Th2-type response   (MGI Ref ID J:25215)
  • renal/urinary system phenotype
  • expanded mesangial matrix
    • 7 of 20 homozygotes exhibit an increase in mesangial matrix   (MGI Ref ID J:25215)
  • glomerulonephritis   (MGI Ref ID J:25215)
  • mesangial cell hyperplasia
    • 7 of 20 homozygotes exhibit an increase in mesangial cells   (MGI Ref ID J:25215)
  • renal glomerulus hypertrophy
    • 7 of 20 homozygotes show enlarged glomeruli   (MGI Ref ID J:25215)
  • adipose tissue phenotype
  • abnormal adipose tissue physiology
    • adult fed female homozygotes show a 42% reduction in adipose tissue cAMP levels relative to wild-type mice   (MGI Ref ID J:52286)
    • impaired lipolysis i.e. FFA release from mutant periovarian fat-pads is most likely due to inability to generate cAMP in response to epinephrine   (MGI Ref ID J:52286)
  • decreased gonadal fat pad weight
    • at 16-20 weeks, adult homozygotes show a ~38% reduction in gonadal fat pad weight relative to wild-type mice   (MGI Ref ID J:62132)
  • decreased percent body fat
    • 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   (MGI Ref ID J:62132)
  • decreased uterine fat pad weight
    • 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   (MGI Ref ID J:52286)
  • integument phenotype
  • skin lesions
    • homozygotes raised under SPF conditions develop skin lesions with increasing age   (MGI Ref ID J:25215)
    • skin lesions are more frequent and severe and appear earlier in homozygotes exposed to pathogens   (MGI Ref ID J:25215)
  • growth/size/body phenotype
  • decreased percent body fat
    • 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   (MGI Ref ID J:62132)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Cebpbtm1Vpo/Cebpb+

        involves: 129S/SvEv * C57BL/6 * MF1
  • endocrine/exocrine gland phenotype
  • abnormal mammary gland duct morphology
    • at maturity (8-12 weeks), ~20% of virgin female heterozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds   (MGI Ref ID J:48513)
    • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of the ductal epithelium   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)
  • integument phenotype
  • abnormal mammary gland duct morphology
    • at maturity (8-12 weeks), ~20% of virgin female heterozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds   (MGI Ref ID J:48513)
    • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of the ductal epithelium   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)

Cebpbtm1Vpo/Cebpbtm1Vpo

        involves: 129S/SvEv * C57BL/6 * MF1
  • endocrine/exocrine gland phenotype
  • abnormal mammary gland development
    • all virgin female homozygotes exhibit abnormal mammary ductal development   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)
    • abnormal branching of the mammary ductal tree
      • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching   (MGI Ref ID J:48513)
      • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes   (MGI Ref ID J:48513)
  • abnormal mammary gland duct morphology
    • 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   (MGI Ref ID J:48513)
    • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)
    • abnormal branching of the mammary ductal tree
      • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching   (MGI Ref ID J:48513)
      • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes   (MGI Ref ID J:48513)
  • abnormal mammary gland physiology
    • 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%   (MGI Ref ID J:48513)
  • reproductive system phenotype
  • female infertility
    • female homozygotes are sterile   (MGI Ref ID J:48513)
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis   (MGI Ref ID J:49673)
    • abnormal gluconeogenesis
      • after partial hepatectomy, homozygotes show abnormal expression of a subset of genes involved in hepatocyte gluconeogenesis   (MGI Ref ID J:49673)
    • hypoglycemia
      • 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   (MGI Ref ID J:49673)
      • in contrast, serum cholesterol and triglyceride levels show no significant differences posthepatectomy   (MGI Ref ID J:49673)
  • liver/biliary system phenotype
  • decreased liver regeneration
    • 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   (MGI Ref ID J:49673)
    • no significant differences in the rate of liver mass reconstitution are observed, suggesting that increased cellular size may be independent of DNA synthesis   (MGI Ref ID J:49673)
    • 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   (MGI Ref ID J:49673)
  • integument phenotype
  • abnormal mammary gland development
    • all virgin female homozygotes exhibit abnormal mammary ductal development   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)
    • abnormal branching of the mammary ductal tree
      • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching   (MGI Ref ID J:48513)
      • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes   (MGI Ref ID J:48513)
  • abnormal mammary gland duct morphology
    • 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   (MGI Ref ID J:48513)
    • ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells   (MGI Ref ID J:48513)
    • 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   (MGI Ref ID J:48513)
    • abnormal branching of the mammary ductal tree
      • at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching   (MGI Ref ID J:48513)
      • following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes   (MGI Ref ID J:48513)
  • abnormal mammary gland physiology
    • 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%   (MGI Ref ID J:48513)

Cebpbtm1Vpo/Cebpbtm1Vpo

        FVB.129S-Cebpbtm1Vpo
  • cellular phenotype
  • decreased apoptosis
    • MEFs exhibit delayed onset of cell death and detachment from the plate after challenge with tunicamycin, an ER stressor, compared to controls   (MGI Ref ID J:52729)
View Research Applications

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

Cardiovascular Research
Other
      altered fat metabolism
      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, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects
      hematopoietic development

Metabolism Research
Lipid Metabolism

Reproductive Biology Research
Fertility Defects
      females only

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cebpbtm1Vpo
Allele Name targeted mutation 1, Valeria Poli
Allele Type Targeted (Null/Knockout)
Common Name(s) C/EBPb-; C/EBPbeta-; Cebpb-;
Mutation Made By Valeria Poli,   University of Dundee
Strain of Origin129S/SvEv-Gpi1
ES Cell Line NameCCE/EK.CCE
ES Cell Line Strain129S/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; LIP; NF-IL6; NF-M; Nfil6; TCF5; nuclear protein Il6;
General Note Phenotypic Similarity to Human Syndrome: Multi-centric Castleman's Disease (J:25215)
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 Western blots of hepatic tissue nuclear extracts. [MGI Ref ID J:25215]

Genotyping

Genotyping Information

Genotyping Protocols

Cebpbtm1Vpo, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

Cebpbtm1Vpo related

Bostrom P; Mann N; Wu J; Quintero PA; Plovie ER; Panakova D; Gupta RK; Xiao C; MacRae CA; Rosenzweig A; Spiegelman BM. 2010. C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell 143(7):1072-83. [PubMed: 21183071]  [MGI Ref ID J:170587]

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; Chojkier M. 2011. C/EBPbeta-Thr217 phosphorylation signaling contributes to the development of lung injury and fibrosis in mice. PLoS One 6(10):e25497. [PubMed: 21998664]  [MGI Ref ID J:178116]

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]

Hayashi Y; Hirai H; Kamio N; Yao H; Yoshioka S; Miura Y; Ashihara E; Fujiyama Y; Tenen DG; Maekawa T. 2013. C/EBPbeta promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. Leukemia 27(3):619-28. [PubMed: 22948537]  [MGI Ref ID J:196803]

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]

Kajimura S; Seale P; Kubota K; Lunsford E; Frangioni JV; Gygi SP; Spiegelman BM. 2009. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 460(7259):1154-8. [PubMed: 19641492]  [MGI Ref ID J:152000]

Kfoury N; Kapatos G. 2009. Identification of neuronal target genes for CCAAT/enhancer binding proteins. Mol Cell Neurosci 40(3):313-27. [PubMed: 19103292]  [MGI Ref ID J:146920]

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]

Pennini ME; Liu Y; Yang J; Croniger CM; Boom WH; Harding CV. 2007. CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein. J Immunol 179(10):6910-8. [PubMed: 17982082]  [MGI Ref ID J:153860]

Rahman SM; Choudhury M; Janssen RC; Baquero KC; Miyazaki M; Friedman JE. 2013. CCAAT/enhancer binding protein beta deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis. Biochem Biophys Res Commun 430(1):336-9. [PubMed: 23159614]  [MGI Ref ID J:193736]

Rahman SM; Janssen RC; Choudhury M; Baquero KC; Aikens RM; de la Houssaye BA; Friedman JE. 2012. CCAAT/enhancer-binding protein beta (C/EBPbeta) expression regulates dietary-induced inflammation in macrophages and adipose tissue in mice. J Biol Chem 287(41):34349-60. [PubMed: 22902781]  [MGI Ref ID J:191771]

Satake S; Hirai H; Hayashi Y; Shime N; Tamura A; Yao H; Yoshioka S; Miura Y; Inaba T; Fujita N; Ashihara E; Imanishi J; Sawa T; Maekawa T. 2012. C/EBPbeta is involved in the amplification of early granulocyte precursors during candidemia-induced "emergency" granulopoiesis. J Immunol 189(9):4546-55. [PubMed: 23024276]  [MGI Ref ID J:190605]

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]

Schwegmann A; Guler R; Cutler AJ; Arendse B; Horsnell WG; Flemming A; Kottmann AH; Ryan G; Hide W; Leitges M; Seoighe C; Brombacher F. 2007. Protein kinase C delta is essential for optimal macrophage-mediated phagosomal containment of Listeria monocytogenes. Proc Natl Acad Sci U S A 104(41):16251-6. [PubMed: 17913887]  [MGI Ref ID J:145217]

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]

Straccia M; Dentesano G; Valente T; Pulido-Salgado M; Sola C; Saura J. 2013. CCAAT/Enhancer binding protein beta regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells. Glia 61(10):1607-19. [PubMed: 23893854]  [MGI Ref ID J:199563]

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]

Wittenmayer N; Korber C; Liu H; Kremer T; Varoqueaux F; Chapman ER; Brose N; Kuner T; Dresbach T. 2009. Postsynaptic Neuroligin1 regulates presynaptic maturation. Proc Natl Acad Sci U S A 106(32):13564-9. [PubMed: 19628693]  [MGI Ref ID J:152008]

Zhang Y; Ma X. 2010. Triptolide inhibits IL-12/IL-23 expression in APCs via CCAAT/enhancer-binding protein alpha. J Immunol 184(7):3866-77. [PubMed: 20194724]  [MGI Ref ID J:160081]

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           FGB27

Colony Maintenance

Breeding & HusbandryWhen 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)   28-NOV-07
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Cebpbtm1Vpo  
Price per Pair (US dollars $)Pair Genotype
$311.00Heterozygous for Cebpbtm1Vpo x Wild-type for Cebpbtm1Vpo  
$311.00Wild-type for Cebpbtm1Vpo x Heterozygous for Cebpbtm1Vpo  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Cebpbtm1Vpo  
Price per Pair (US dollars $)Pair Genotype
$404.30Heterozygous for Cebpbtm1Vpo x Wild-type for Cebpbtm1Vpo  
$404.30Wild-type for Cebpbtm1Vpo x Heterozygous for Cebpbtm1Vpo  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

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   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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