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Pancreatic MODY3

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info@definigen.com
UK +44 (0)1223 497106
USA 617-674-3260

DefiniGEN provide disease modelled MODY3 diabetes human pancreatic cells which are highly functional CRISPR gene-edited human pancreatic cells. Neonatal diabetes mellitus (NDM) is a rare but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. The neonatal diabetes cell products display the disease phenotype in combination with general function comparable to human primary pancreatic islets. These cell products can offer disease modelling and drug discovery researchers unprecedented tool for elucidating the underlying mechanisms of this key form of monogenic diabetes.

  • Highly standardized cell product containing >97% human pancreatic cells with consistent performance and biologically relevant data
  • Disease circuit verified confirmed mutation in the HNF1-alpha transcription factor gene – insertion of C at codon 872 producing a  frameshift mutation
  • Phenotypic analysis of the cells using GSIS assays demonstrates that the insulin response to glucose challenge is dysfunctional in these disease modelled cell products in contrast to DefiniGEN’s isogenic wild-type control pancreatic cell products.

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Def-PANC MODY3 Cell Morphology

Genetic information and phenotypic response confirm Def-PANC MODY3 cells are an effective model of Monogenic Diabetes.

 

MODY3 diabetes pancreatic cells diplay altered morphology in both monolayer and islet culture

Figure 1. Def-PANC MODY3 cells display aberrant morphology in both monolayer and islet culture.

Disease Circuit Verification

MODY3 pancreatic disease model with mutation in HNF1-alpha transcription factor gene – insertion of C at codon 872 producing frameshift mutation – isogenic control available.

 

MODY3 pancreatic disease model with mutation in HNF1-alpha transcription factor gene - insertion of C at codon 872 producing frameshift mutation

Figure 2. P291 in exon 4. Insertion of C Heterozygous line available

GLUT + PKLR Expression Analysis

 

GLUT-2 gene expression is dimished in heterozygous HNF1a pancreatic cells and ablated in homozygous HNF1a cells.

PKLR gene expression is dimished in heterozygous HNF1a pancreatic cells and ablated in homozygous HNF1a cells

Figure 3. Heterozygous and homozygous Def-PANC MODY3 cells show progressive gene change effects in key HNF1a gene regulated genes including PKLR and GLUT-2.

Pancreatic Key Marker Analysis

 

Key marker analysis by qPCR shows reduction in key pancreatic cell markers

Figure 4. Key marker analysis by qPCR shows reduction in key pancreatic cell markers in the Def-PANC disease models.

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For further information please contact us:

info@definigen.com