Draft:N2G mouse

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The N2G mouse (NOD–2–Genes knockout) is a severely immunodeficient laboratory mouse strain developed on a NOD background. The strain was generated by GEMCRO Inc. (South Korea) using CRISPR/Cas9 to delete large genomic regions of Prkdc, which encodes DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and Il2rg, which encodes the interleukin-2 receptor common gamma chain (γc).[1]

Genetics and immunophenotype

Loss of Prkdc function disrupts V(D)J recombination, resulting in the absence of mature T and B lymphocytes. Deletion of Il2rg additionally prevents natural killer cell development. The combined deficiency produces a T−B−NK− phenotype comparable to that of the NSG mouse and NOG mouse strains, which carry loss-of-function mutations in the same two genes.[1][2][3]

Applications

Human cancer xenografts

N2G mice support subcutaneous engraftment of human cancer cell lines and have been used to evaluate targeted therapies in vivo. The strain has been employed to investigate aurora kinase B inhibition as a strategy to overcome resistance to MET-targeted drugs in MET-amplified lung cancer models.[4] In a separate study, N2G mice were used to examine the role of dysfunctional adipocytes in tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.[5]

Hematopoietic stem cell engraftment

The strain supports engraftment of human hematopoietic stem cells (HSCs) and subsequent reconstitution of human immune cell populations.[1]

Cell therapy evaluation

A derivative strain, N2G-F8, carries an additional deletion of the F8 gene and has been used to evaluate iPSC-derived cell therapies for haemophilia A. A functionally enhanced factor VIII gene integrated into the AAVS1 locus of patient-derived iPSCs was assessed in N2G-F8 mice.[6]

See also

References

Bibliography