huCIDEB(2) Mouse
Product Name
huCIDEB(2) Mouse
Product ID
C001990
Strain Name
C57BL/6JCya-Cidebem1Gt(ROSA)26Sortm1(hCIDEB)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “huCIDEB(2) Mouse (Catalog C001990) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
CIDEB
Gene Alias
--
NCBI ID
Chromosome
Chr 14 (Human)
MGI ID
Datasheet
Strain Description
The CIDEB (Cell Death Inducing DFFA Like Effector B) gene encodes a lipid transferase protein that is predominantly expressed in the liver, but also found in significant levels in the small intestine, colon, kidney, and spleen. This protein primarily localizes to the cytosol, perinuclear region of the cytoplasm, and specifically to lipid droplets and the endoplasmic reticulum, where it plays a critical role in lipid metabolism by promoting the fusion of lipid droplets to form larger unilocular droplets, thereby favoring lipid storage and restricting lipolysis [1]. CIDEB is also essential for the lipidation and maturation of very-low-density lipoproteins (VLDLs) and chylomicrons, facilitating their transport [2]. Beyond lipid metabolism, CIDEB has been implicated in the positive regulation of apoptosis, though its basal expression levels do not typically induce cell death [3]. Furthermore, CIDEB influences the replication cycle of hepatitis C virus (HCV) and hepatitis B virus (HBV), acting as a cofactor for HCV entry into hepatocytes [4]. Associated diseases include various liver conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), with rare germline loss-of-function variants in CIDEB demonstrating a protective effect against these liver diseases [5].
The huCIDEB(2) mouse is a humanized model generated by cloning the sequence upstream of human CIDEB exon 1 to downstream of exon 5 in reverse orientation into intron 1 of the ROSA26 gene, and simultaneously knocking out mouse Cideb exon 2. huCIDEB(2) mice can be used for research into the pathogenesis of various liver conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV). They are also useful for the screening, development, and safety evaluation of CIDEB-targeted drugs. Cyagen also offers a related model: the huCIDEB(1) Mouse (Catalog No.: C001803). The huCIDEB(1) mouse utilizes a mouse gene in situ replacement strategy, employing the endogenous mouse promoter to drive human CIDEB (covering exon 1 to exon 5). This results in negligible expression of the adjacent gene Ltb4r2 and low levels of human CIDEB mRNA. In contrast, the huCIDEB(2) mouse (Catalog No.: C001990) uses the human promoter to drive the complete human CIDEB sequence including upstream and downstream regulatory regions, thereby preserving normal Ltb4r2 expression and achieving robust human CIDEB mRNA expression.
Reference
Xu L, Li L, Wu L, Li P, Chen FJ. CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth. FEBS Lett. 2024 May;598(10):1154-1169.
Ye J, Li JZ, Liu Y, Li X, Yang T, Ma X, Li Q, Yao Z, Li P. Cideb, an ER- and lipid droplet-associated protein, mediates VLDL lipidation and maturation by interacting with apolipoprotein B. Cell Metab. 2009 Feb;9(2):177-90.
Wutsdorff L, Mougnekabol J, Tang P, Reutzel-Selke A, Sauer IM, Haep N. Unveiling the Multifaceted Role of CIDEB: From Apoptosis to Lipid Metabolism and Liver Health. Livers. 2024; 4(3):406-419.
Wu X, Lee EM, Hammack C, Robotham JM, Basu M, Lang J, Brinton MA, Tang H. Cell death-inducing DFFA-like effector b is required for hepatitis C virus entry into hepatocytes. J Virol. 2014 Aug;88(15):8433-44.
Verweij N, Haas ME, Nielsen JB, Sosina OA, Kim M, Akbari P, De T, Hindy G, Bovijn J, Persaud T, Miloscio L, Germino M, Panagis L, Watanabe K, Mbatchou J, Jones M, LeBlanc M, Balasubramanian S, Lammert C, Enhörning S, Melander O, Carey DJ, Still CD, Mirshahi T, Rader DJ, Parasoglou P, Walls JR, Overton JD, Reid JG, Economides A, Cantor MN, Zambrowicz B, Murphy AJ, Abecasis GR, Ferreira MAR, Smagris E, Gusarova V, Sleeman M, Yancopoulos GD, Marchini J, Kang HM, Karalis K, Shuldiner AR, Della Gatta G, Locke AE, Baras A, Lotta LA. Germline Mutations in CIDEB and Protection against Liver Disease. N Engl J Med. 2022 Jul 28;387(4):332-344.
Strain Strategy
The sequence from upstream of exon 1 of the human CIDEB gene to downstream of exon 5 of the human CIDEB gene was cloned into intron 1 of ROSA26 in reverse orientation. The Cideb gene contains five exons, with the ATG start codon located in exon 1 and the TAA stop codon located in exon 5. The coding region of exon 2 was selected as the target site.
Figure 1. Gene editing strategy of huCIDEB(2) mice.
Figure 2. Diagram of the murine gene knockout in huCIDEB(2) mice.
Application Area
CIDEB-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of various liver conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV);
Research on cell apoptosis and hepatocellular injury;
Research on metabolic syndrome, obesity, and other lipid metabolism-related diseases.
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