Phenotypes associated with this allele

• Allele Symbol: Cebpa^tm1Gjd
• Allele Name: targeted mutation 1, Gretchen J Darlington
• Allele ID: MGI:2177053
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cebpa^tm1Gjd/Cebpa^tm1Gjd	B6.129S7-Cebpa^tm1Gjd	MGI:3525188
hm2	Cebpa^tm1Gjd/Cebpa^tm1Gjd	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6	MGI:3612269
hm3	Cebpa^tm1Gjd/Cebpa^tm1Gjd	involves: 129S7/SvEvBrd * C57BL/6	MGI:2177059

Genotype
MGI:3525188

hm1

• Allelic Composition: Cebpa^tm1Gjd/Cebpa^tm1Gjd
• Genetic Background: B6.129S7-Cebpa^tm1Gjd

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

hematopoietic system

absent common myeloid progenitor cells ( J:94682 )

• granulocyte/monocyte progenitors are almost completely absent, however megakaryocyte/erythrocyte progenitor cell numbers are increased

failure of myelopoiesis ( J:94682 )

• in vitro common myeloid progenitor cells fail to form any mature granulocyte-macrophage, macrophage, or granulocytic colonies

immune system

failure of myelopoiesis ( J:94682 )

• in vitro common myeloid progenitor cells fail to form any mature granulocyte-macrophage, macrophage, or granulocytic colonies

Genotype
MGI:3612269

hm2

• Allelic Composition: Cebpa^tm1Gjd/Cebpa^tm1Gjd
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:48513 )

N • mammary outgrowths isolated from newborn mutant mammary epithelium and transplanted into cleared mammary fat pads of syngeneic hosts show no detectable differences in ductal morphogenesis, lobuloalveolar proliferation or functional differentiation in the mammary gland

reproductive system

reproductive system phenotype ( J:48513 )

N • mammary outgrowths isolated from newborn mutant mammary epithelium and transplanted into cleared mammary fat pads of syngeneic hosts show no detectable differences in ductal morphogenesis, lobuloalveolar proliferation or functional differentiation in the mammary gland

Genotype
MGI:2177059

hm3

• Allelic Composition: Cebpa^tm1Gjd/Cebpa^tm1Gjd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Lack of mature neutrophils in Cebpa^tm1Gjd/Cebpa^tm1Gjd mice

mortality/aging

neonatal lethality, complete penetrance ( J:28320 )

• if left untreated, homozygotes die by 8 hrs post-partum from hypoglycemia

• hypoglycemic newborns can be maintained until P2 by subcutaneous injections of glucose but rarely survive beyond 40 hrs, despite normal suckling behavior and presence of normal volumes of gastric milk

perinatal lethality, incomplete penetrance ( J:28320 )

• most homozygotes survive to term; however, homozygotes are obtained at a reduced frequency at birth (20.5% vs 25%), indicating embryonic/perinatal loss

digestive/alimentary system

digestive/alimentary phenotype ( J:46862 )

N • newborn homozygotes transiently rescued by glucose injections exhibit normal structural and functional maturation of the small intestine, with no significant differences in mucosal architecture or in the size of proliferative zone in intestinal crypts

growth/size/body

decreased body weight ( J:28320 )

• at 32 hrs post-partum, glucose-treated homozygotes fail to increase their birth weights as efficiently as wild-type or heterozygous mutant mice (~9.6% vs ~32.4%)

slow postnatal weight gain ( J:28320 )

• newborn homozygotes transiently rescued by glucose injections gain little weight relative to wild-type mice

homeostasis/metabolism

increased circulating tyrosine level ( J:28320 )

• at 32 hrs post-partum, homozygotes show a ~4-fold increase in serum tyrosine levels relative to wild-type mice

decreased circulating serum albumin level ( J:28320 )

• at 2 hrs post-partum, homozygotes display a 50% reduction in albumin mRNA levels relative to wild-type mice; levels remain low at 7 and 32 hrs post-partum

abnormal energy expenditure ( J:28320 )

• newborn homozygotes exhibit severe derangements of energy metabolism resulting from a lack of triacylglycerol storage in adipose tissue and glycogen storage in the liver

abnormal glucose homeostasis ( J:28320 )

hypoglycemia ( J:28320 )

• homozygotes exhibit reduced glucose concentrations as early as 1-2 hrs post-partum, and remain hypoglycemic at 5-8 hrs with glucose concentrations of only 0.61.3 mg/dl

• neonatal hypoglycemia is partly attributed to an observed delay in transactivation of PEPCK and G6Pase

abnormal gluconeogenesis ( J:28320 )

• homozygotes exhibit delayed transactivation of PEPCK and G6Pase

abnormal glycogen homeostasis ( J:28320 )

• homozygotes exhibit impaired prenatal and postnatal glycogen synthesis

decreased liver glycogen level ( J:28320 )

• at E18.5 and at 1 hr post-partum, homozygotes contain virtually no glycogen in the liver, whereas wild-type mice contain abundant glycogen

• at 32 hrs post-partum, glucose-injected homozygotes fail to exhibit abundant hepatic glycogen

• absence of hepatic glycogen is associated with a 50-70% reduction in glycogen synthase mRNA

abnormal lipid homeostasis ( J:28320 )

• homozygotes show lack of triacylglycerol storage in adipose tissue, probably as a result of abnormal lipid processing or storage

respiratory system

abnormal lung morphology ( J:28320 )

• histologically, mutant lungs appear immature relative to wild-type lungs

abnormal pulmonary alveolus morphology ( J:105087 )

• neonatal mutant lungs display excessive accumulation of surfactant material in the alveoli

increased type II pneumocyte number ( J:105087 )

• neonatal mutant lungs exhibit hyperproliferation of alveolar type II (SP-C-positive) cells

abnormal pulmonary alveolus wall morphology ( J:105087 )

• neonatal mutant lungs display a significantly hyperplastic alveolar wall with many alveolar cells

abnormal surfactant secretion ( J:105087 )

• neonatal mutant lungs display overexpression of surfactant protein SP-A, SP-B and SP-C mRNAs as determined by immunohistochemistry, in situ hybridization, and Northern blot analysis

behavior/neurological

lethargy ( J:28320 )

• homozygotes exhibit lethargy several hours after birth

• however, mutant neonates appear grossly normal with no significant alterations in major organ morphology or birth weights

absent gastric milk in neonates ( J:28320 )

• mutant pups contain little or no milk in their stomachs, probably as a result of lack of energy for nourishment

adipose tissue

decreased brown adipose tissue amount ( J:28320 )

• at 32 hrs post-partum, homozygotes fail to display an increase in the volume of interscapular brown adipose tissue; no large lipid droplets are observed, suggesting abnormal adipocyte maturation

• in addition, the expression of the Ucp1 gene for uncoupling protein-1, a marker of brown adipose tissue, is reduced

decreased white adipose tissue amount ( J:28320 )

abnormal inguinal fat pad morphology ( J:28320 )

• at 15 min and 32 hrs post-partum, homozygotes fail to show lipid accumulation in subcutaneous inguinal white adipose tissue

liver/biliary system

abnormal liver morphology ( J:28320 )

• at 32 hrs post-partum, glucose-injected homozygotes exhibit hepatocytes with reduced lipid accumulation and glycogen storage relative to wild-type mice

• no significant differences in serum alanine transaminase or alanine phosphatase activities are observed, indicating absence of hepatic injury or necrosis

• no bile thrombi or cholestasis are observed

decreased liver glycogen level ( J:28320 )

• at E18.5 and at 1 hr post-partum, homozygotes contain virtually no glycogen in the liver, whereas wild-type mice contain abundant glycogen

• at 32 hrs post-partum, glucose-injected homozygotes fail to exhibit abundant hepatic glycogen

• absence of hepatic glycogen is associated with a 50-70% reduction in glycogen synthase mRNA

abnormal hepatocyte morphology ( J:28320 )

• mutant hepatocyte rosettes display decreased cellular volumes and dilated biliary canaliculi with shorter and fewer microvilli than wild-type mice

• as a result, mitochondria and the endoplasmic reticulum appear densely packed