Phenotypes Associated with This Genotype

Genotype
MGI:2656637

• Allelic Composition: Cebpb^tm1Kish/Cebpb^tm1Kish
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

perinatal lethality, incomplete penetrance ( J:77003 )

• homozygotes are obtained at a lower frequency than the expected Mendelian ratio, suggesting prenatal and perinatal lethality

neonatal lethality, incomplete penetrance ( J:45062 )

• ~35% of homozygotes die within 24 hrs after birth, with no significant increase in mortality thereafter

• the % of homozygotes is closer to the expected Mendelian ratio at 10 hrs after birth (22.4% vs 25%)

postnatal lethality, incomplete penetrance ( J:45062 , J:77003 )

• at 4 weeks, the % of homozygotes obtained is only 16.2% (J:45062)

• born homozygotes appear healthy and show no significant increase in mortality or histological abnormalities under SPF conditions; however, a number of homozygotes become compromised and die under conventional conditions (J:77003)

craniofacial

abnormal zygomatic arch morphology ( J:237461 )

• downward tilted zygomatic arch; zygomatic arch deformation is limited to the zygoma and not involved with the zygomatic processes of the maxilla and/or the squamosal bone

reproductive system

female infertility ( J:45062 )

♀ • female homozygotes are infertile

skeleton

abnormal zygomatic arch morphology ( J:237461 )

• downward tilted zygomatic arch; zygomatic arch deformation is limited to the zygoma and not involved with the zygomatic processes of the maxilla and/or the squamosal bone

abnormal clavicle morphology ( J:237461 )

• shorter and thinner clavicles

• however, mice exhibit normal limb joints

abnormal thoracic cage morphology ( J:237461 )

• narrow thoracic cage

immune system

abnormal macrophage physiology ( J:77003 )

• in vitro, LPS-stimulated mutant peritoneal macrophages and fibroblasts exhibit impaired G-CSF mRNA induction as well as reduced G-CSF biological activity

• in vitro, mutant activated peritoneal macrophages (but not neutrophils) exhibit suppressed production of superoxide and hydrogen peroxide relative to wild-type macrophages

• despite normal nitric oxide (NO) production, mutant peritoneal macrophages display severely impaired listericidal activity even when maximally activated in vitro with IFN-gamma plus LPS

• in vitro, mutant activated peritoneal macrophages exhibit extremely reduced tumoricidal and tumoristatic activity against P815 mastrocytoma target cells

impaired macrophage phagocytosis ( J:77003 )

• during listeriosis, homozygotes fail to retain L. monocytogenes effectively within their phagosomes, even when maximally activated in vitro with IFN-gamma plus LPS, with 84% of bacteria abnormally localized in the cytoplasm instead of in vacuoles

increased interleukin-12 secretion ( J:126085 )

• macrophages stimulated with LPS, BLP, MALP-2, or CpG DNA produce more IL12p40 compared with similarly treated wild-type cells

increased susceptibility to bacterial infection ( J:77003 )

• despite normal TNF and IFN-gamma induction, homozygotes succumb to sublethal doses of Listeria monocytogenes, with a 100% mortality rate within 5 days of i.p. inoculation and focal accumulation of neutrophils and macrophages in the liver and spleen

• in addition, homozygotes are highly susceptible to sublethal doses of Salmonella typhimurium, with a 100% mortality rate within 6 days of i.p. injection and a similar focal accumulation of inflammatory cells in the liver and spleen

adipose tissue

abnormal brown adipose tissue morphology ( J:45062 )

• at 20 hrs after birth, newborn homozygotes exhibit a significantly reduced intracytoplasmic lipid content in intercapsular brown adipocytes

• in mutant BAT, the presence of only small lipid droplets suggests that adipocyte differentiation is blocked at the immature adipocyte stage

cellular

abnormal cell differentiation ( J:45062 )

• in response to hormonal stimulants, mutant embryonic fibroblasts show a significant reduction in adipogenic differentiation and accumulation of lipid droplets relative to wild-type fibroblasts

impaired macrophage phagocytosis ( J:77003 )

• during listeriosis, homozygotes fail to retain L. monocytogenes effectively within their phagosomes, even when maximally activated in vitro with IFN-gamma plus LPS, with 84% of bacteria abnormally localized in the cytoplasm instead of in vacuoles

hematopoietic system

abnormal macrophage physiology ( J:77003 )

• in vitro, LPS-stimulated mutant peritoneal macrophages and fibroblasts exhibit impaired G-CSF mRNA induction as well as reduced G-CSF biological activity

• in vitro, mutant activated peritoneal macrophages (but not neutrophils) exhibit suppressed production of superoxide and hydrogen peroxide relative to wild-type macrophages

• despite normal nitric oxide (NO) production, mutant peritoneal macrophages display severely impaired listericidal activity even when maximally activated in vitro with IFN-gamma plus LPS

• in vitro, mutant activated peritoneal macrophages exhibit extremely reduced tumoricidal and tumoristatic activity against P815 mastrocytoma target cells

impaired macrophage phagocytosis ( J:77003 )

• during listeriosis, homozygotes fail to retain L. monocytogenes effectively within their phagosomes, even when maximally activated in vitro with IFN-gamma plus LPS, with 84% of bacteria abnormally localized in the cytoplasm instead of in vacuoles

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteochondrodysplasia		DOID:2256		J:237461