Dysfunctional PRKDC gene leads to impaired development of T and B lymphocytes which gives rise to severe combined immunodeficiency (SCID).
Commonly utilized strains included BALB/c-nu, Swiss-nu, NC-nu, and NIH-nu, which were extensively employed in the research of immune diseases and tumors.
The next big step in the development of humanized mice models came with transfer of the scid mutation to a non-obese diabetic mouse.
This accounted for the creation of the NOD-scid-γcnull mice (NCG, NSG or NOG) models which were found to have defective signaling of interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.
[8] These studies have highlighted the effectiveness of the hu-PBL-SCID mouse model in examining various facets of human diseases, including pathogenesis, immune responses, and therapeutic interventions.
Furthermore, the model has been utilized to explore genetic and molecular factors linked to neuropsychiatric disorders such as schizophrenia, offering valuable insights into the pathophysiology and potential therapeutic targets for these conditions.
This model has been instrumental in studying the human immune response to xenogeneic and allogeneic decellularized biomaterials, providing valuable insights into the biocompatibility and gene expression regulation of these materials.
The cells are obtained from human fetal liver, bone marrow or from blood derived from the umbilical cord,[12] and engrafted via intravenous injection.
Nevertheless, limitations associated with the model are that it takes a minimum of 10 weeks for cell differentiation to occur, it harbors low levels of human RBCs, polymorphonuclear leukocytes, and megakaryocytes.
Other drawbacks associated with the model are that it portrays weak immune responses to xenobiotics, sub-optimal class switching and may develop GvHD.
[7] Bio- and electrical engineers have shown that human cerebral organoids transplanted into mice functionally integrate with their visual cortex.
[27] PDX models are considered to retain the parental malignancy characteristics at a greater extent and hence these are regarded as the more powerful tool for evaluating the effect of anticancer drugs in pre-clinical studies.
For instance, humanized mice have been utilized to study human-tropic pathogens, liver cancer models, and the comparison of mouse models to human diseases NSG mice engrafted with PBMCs and administered with myelin antigens in Freund's adjuvant, and antigen-pulsed autologous dendritic cells have been used to study multiple sclerosis.
[33] Similarly, NSG mice engrafted with hematopoietic stem cells and administered with pristane have been used for studying lupus erythematosus.
[35] The development of humanized mouse models has significantly advanced the study of autoimmune disorders and various areas of immunology and disease research.