Basic Information

Strain Name
C57BL/6-Cd38tm3(CD38)/Bcgen
Stock Number
110046
Common Name
B-hCD38 mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
CD38, ADPRC 1, ADPRC1
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous

Description

CD38 is a 42 kD glycoprotein, also known as T10. It is an ADP-ribosyl hydrolase, expressed on B cells, NK cells, a subset of T cells, brain, muscle, and kidney. In mouse, CD38 expression is downregulated on germinal center B cells and plasma cells, whereas this is not the case for humans. By functioning as both a cyclase and a hydrolase, CD38 mediates lymphocyte activation, as well as adhesion and metabolism of cADPR and NAADP. CD31 is also the ligand of CD38. NAD+ is disassembled into byproducts that flow in the BM plasma fluid within the myeloma niche, accumulating variable amounts of ADO. Most of ADO is taken-up by purinergic cell receptors (ADOR) expressed by bone cells or immune cells inside the niche. The outcome is either a block of the effectiveness of immune cells (Teff, NK, TAMs) that are capable of destroying tumor cells or that increase the number of regulatory T-cells (Tregs), mesenchymal derived stromal cells (MDSC), or dendritic cells (DC) which suppress immune cells from responding to the tumor. Increased expression of CD38 is an unfavourable diagnostic marker in chronic lymphocytic leukemia and is associated with increased disease progression. CD38 is also used as a target for daratumumab (Darzalex), a medicine that has been approved for the treatment of multiple myeloma.

Details

Protein expression analysis

Strain specific CD38 expression analysis in heterozygous B-hCD38 mice by flow cytometry. Splenocytes were collected from WT and heterozygous B-hCD38 (H/+) mice, and analyzed by flow cytometry with species-specific anti-CD38 antibody. Mouse CD38 was detectable in WT and heterozygous B-hCD38 mice. Human CD38 was exclusively detectable in heterozygous B-hCD38 but not WT mice.

Protein expression analysis

Strain specific CD38 expression analysis in homozygous B-hCD38 mice by flow cytometry. Splenocytes and blood were collected from WT and homozygous B-hCD38 (H/H) mice, and analyzed by flow cytometry with species-specific anti-CD38 antibody. Mouse CD38 was detectable in WT mice. Human CD38 was exclusively detectable in homozygous B-hCD38 but not WT mice.

B-CAG-hCD38 MC38 bind anti-human CD38 antibody

Analysis of B-CAG-hCD38 MC38 by FACS. Flow cytometry analysis of the B-CAG-hCD38 MC38 was performed to assess anti-human CD38 Ab binding. Single live cells were gated for CD45 population and used for further analysis as indicated here. B-CAG-hCD38 MC38 can bind well to anti-hCD38 antibody (daratumumab, in house) vs isotype control.

B cells in B-hCD38 mice bind anti-human CD38 antibody

Analysis of splenocytes of B-hCD38 mice by FACS. Splenocytes were isolated from female B-hCD38 mice (6 week-old). Flow cytometry analysis of the splenocytes was performed to assess anti-human CD38 Ab binding with Splenocytes. Single live cells were gated for CD45 population and used for further analysis as indicated here. Splenocytes in homozygous B-hCD38 mice can bind well to anti-hCD38 antibody (daratumumab, in house) vs isotype control.

Blood routine test results

Complete blood count (CBC). Blood from C57BL/6 and B-hCD38 mice (n=5, 6 week-old, female and male) were collected and analyzed for CBC. Any measurement of B-hCD38 mice in the panel were similar to C57BL/6, and there was no differences between male and female mice, indicating that humanized mouse does not change blood cell composition and morphology. Values are expressed as mean ± SEM.

Blood chemistry results

Blood chemistry tests of B-hCD38 mice. Serum from C57BL/6 and B-hCD38 mice (n=5, 6 week-old, female and male) were collected and analyzed for levels of ALT, AST and other indicators in the panel. There was no differences on either measurement between C57BL/6 and humanized mouse, indicating that humanized mouse does not change ALT and AST levels or health of liver. Values are expressed as mean ± SEM.

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