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HUmanized Mice for Assays to Normalize Endocrine Pancreas Function

mouse

The scientific goal for the HUMANE CBP is to develop in vivo systems and assays to measure reconstitution of beta cell function. Developing qualitative and/or quantitative clonogenic in vivo assays able to assess the ability of transplanted beta stem or progenitor cells to reconstitute any pancreatice cell lineage in diabetic animals is the focus of the HUMANE CBP. To accomplish this, the HUMANE team is engineering beta-cell ablation models onto immunodeficient mouse strains to allow engraftment of strain-mismatched or species-mismatched stem/progenitors for beta cell reconstitution/clonogenic assays. The long term goal is to provide models for human beta stem and progenitor cells that will also support the development of a human immune system so that human beta cell function can be evaluated in the context of human immunity and autoimmunity.

Investigators

Funding Program



Flow Cytometry Profiles

Parameter NOD/Lt  NOD/Lt NOD-Rag1null NOD-Rag1null
IL2rgnull		 NOD-Rag1null
Prf1null		 NOD-Rag1null
Prf1nullIns2+/Akita		 NOD-Rag1null
IL2rgnullIns2Akita		 NOD-Scid
IL2rgnull
Spleen 50.3 27.7 5.3 (0.5) 5.0(0.4) 18.5(3.8) 32.86(7.9)    
Bone Marrow 65.4       38.7(4.1) 40.36(5.5)    
Surface marker (100%)                
Spleen
CD3+CD4+ 23.4 29 0.3 0.3 0.1 0   0.1
CD3+CD8+ 11.9 11.8 0.1 0.3 0.1 0   0.1
B220+IgK, light chain+ 39.1 40.9 0 0 0.1 0.3   0
B220+IgK, light chain- 2.1 1.8 5.6 6.3 7.9 10.7   6.1
GR-1+/Mac-1+ 5.3 2.7 22 18.1 20.2 23.3   27.9
GR-1+/Mac-1- 4.3 6.3 33.8 14 17.5 23   17.6
Ter 119+ 6.7 1.4 27.7 48.8 32.6 31   20
DX5+CD122+ 1.7 0.5 4.8 0.1 8.6 7.5   0.2
LGL+CD122+ 0.3 0.4 4.3 0.1 3 2.1   0
H-2Kd+I-Ag7- 46.4       67 69.5   98.2
H-2Kd+I-Ag7+ 52       31 25.6   7.8
Total MHC I+   99.7 99.8 95.2        
MHC 1+/MHC II+   55.5 11.7 11.1        
Bone marrow
CD3+CD4+ 0.9       0.3 0.2    
CD3+CD8+ 0.6       0 0    
B220+IgK, light chain+ 7.4       0 0    
B220+IgK, light chain- 12.4       13.4 12.6    
GR-1+/Mac-1+ 58.2       53.4 57.7    
GR-1+/Mac-1- 6       10.5 10.4    
Ter 119+ 9.2       13.9 10.2    
DX5+CD122+ 0.9       2.6 1.9    
LGL+CD122+ 0.2       1 0.5    
H-2Kd+I-Ag7- 63.7       71.2 70.3    
H-2Kd+I-Ag7+ 27.5       26.5 26.6    

 


Attributions

Page authored by Drs. Juli Wu and J.-P. Cartailler of the BCBC Coordinating Center.
The mouse illustration was obtained from the Open Clip Art Library and created by the user known as "Lemmling".