STOCK Cebpb^tm1Vpo/J

Stock number: 006873
Product name: C/EBPβ-
Research areas: Cardiovascular Research, Developmental Biology Research, Diabetes and Obesity Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Metabolism Research, Reproductive Biology Research

Description

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.

Detailed 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-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.

Allele

Symbol: Cebpb^tm1Vpo
Name: targeted mutation 1, Valeria Poli
MGI accession ID: MGI:2149329
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cebpb
Marker name: CCAAT/enhancer binding protein (C/EBP), beta
Chromosome: 2
Strain of origin: 129S/SvEv-Gpi1^c
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.
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).