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Phenotypes Associated with This Genotype
Genotype
MGI:2174941
Allelic
Composition
Cebpbtm1Vpo/Cebpbtm1Vpo
Genetic
Background
involves: 129S/SvEv * MF1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cebpbtm1Vpo mutation (1 available); any Cebpb mutation (10 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• homozygotes raised in a non-specific pathogen-free facility display an additional 50% increase in mortality during the first few weeks post-weaning
• only 12% of homozygotes, instead of the expected Mendelian ratio of 25%, are obtained at weaning, indicating postnatal lethality

hematopoietic system
• 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
• homozygotes show bone marrow hyperplasia with a prevalence of myeloblasts, mature granulocytes and megakaryocytes
• 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
• 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
• starting at 16 weeks of age, homozygotes exhibit splenomegaly
• homozygotes display a hyperplastic white pulp relative to wild-type mice
• 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
• ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice
• 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
• 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
• 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

homeostasis/metabolism
• at 16-20 weeks, reduced adipose tissue mass is associated with significantly reduced plasma leptin levels
• in response to systemic candidiasis, homozygotes fail to exhibit a significant increase in serum IL-12 levels, indicating an impaired Th1 response
• nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age
• 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
• after an 18-hr overnight fast, adult female homozygotes exhibit an ~40% reduction in basal hepatic glucose production (HGP) relative to wild-type mice (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 (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 (J:62132)
• in the fed state, adult female homozygotes exhibit normal plasma glucose levels relative to wild-type mice (J:52286)
• 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 (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 (J:52286)
• after a 6-hr fast, adult homozygotes exhibit a 25% reduction in plasma glucose levels relative to wild-type mice (J:62132)
• after a 6-hr fast, adult homozygotes exhibit a 35% reduction in plasma insulin levels relative to wild-type mice
• adult female homozygotes exhibit reduced gluconeogenesis during fasting
• 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
• 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
• homozygotes exhibit hemosiderosis in the red pulp of the spleen
• 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 (J:52286)
• after an 18-hr overnight fast, adult female homozygotes exhibit a slight increase in circulating corticosterone levels relative to wild-type mice
• 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
• 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 (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 (J:62132)
• after an 18-hr overnight fast, adult female homozygotes show a 31% reduction in circulating triglyceride 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

muscle
• in vitro, skeletal muscles from homozygotes show increased insulin-stimulated glucose transport activity and elevated IRS-1 protein levels

immune system
• 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
• 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
• starting at 16 weeks of age, homozygotes exhibit splenomegaly
• homozygotes display a hyperplastic white pulp relative to wild-type mice
• 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
• in response to systemic candidiasis, homozygotes fail to exhibit a significant increase in serum IL-12 levels, indicating an impaired Th1 response
• nearly all homozygotes (only males studied) exhibit significantly increased serum IL-6 levels, with mean values increasing with age
• homozygotes exhibit enlarged mesenteric lymph nodes relative to wild-type mice
• 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
• homozygotes contain numerous sheets and aggregates of mostly mature plasma cells in the compressed paracortical region of hyperplastic lymph nodes
• homozygotes exhibit an enlarged medulla
• homozygotes exhibit medullary cords packed with sheets and aggregates of mostly mature plasma cells in pseudotumoral arrangement
• starting at 16 weeks of age, homozygotes display enlarged peripheral lymph nodes (lymphoadenopathy)
• homozygotes exhibit enlarged lacrimal and peribronchial lymph nodes relative to wild-type mice
• homozygotes exhibit enlarged inguinal lymph nodes relative to wild-type mice
• starting at 16 weeks of age, homozygotes exhibit mucosal swelling
• 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
• 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
• 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
• ageing homozygotes spontaneously display high levels of IgG-bearing cells relative to wild-type mice
• 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
• 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
• 7 of 20 homozygotes exhibit an increase in mesangial cells
• 7 of 20 homozygotes exhibit an increase in mesangial matrix
• 7 of 20 homozygotes show enlarged glomeruli

adipose tissue
• at 16-20 weeks, adult homozygotes show a ~38% reduction in gonadal fat pad weight relative to wild-type mice
• 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
• 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
• 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

integument
• 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

cellular
• in vitro, skeletal muscles from homozygotes show increased insulin-stimulated glucose transport activity and elevated IRS-1 protein levels

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
viral infectious disease DOID:934 J:25215


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
07/09/2019
MGI 6.14
The Jackson Laboratory