Mice created with full functional human immune systems and human like gut microbiome for the first time

Good news! Will we ever create a human with a fully functional mouse immune system?

Always remember how many thousands if not millions of lab animals were experimented on and have died for our health! Hopefully, we will be able to find a replacement soon!

"For the first time, scientists have successfully created a type of mouse with a 100% functional human immune system and human-like gut microbiome. This 'humanized' mouse takes the guesswork out of medical research and has the potential to revolutionize how we test new drugs and unlock disease mechanisms. ...
team also started with immunodeficient mice (NSG W41 mutants), injecting human stem cells purified from umbilical cord blood through the animal's left ventricle. After a period of weeks to allow this graft to settle, the mice were hormonally conditioned with 17b-estradiol (E2) – estrogen. ..."

"... Many of the more than 1,600 immune response mouse genes, however, are incongruent with their human equivalents, resulting in divergencies or deficiencies of mice as predictors of human immune responses. ..."

From the abstract:

"Humanized mice are limited in terms of modeling human immunity, particularly with regards to antibody responses. Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated KitW-41J mutant immunodeficient pups with human cord blood CD34+ cells, followed by 17β-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyer’s patches, and human thymic epithelial cells. These mice have diverse human B cell and T cell antigen receptor repertoires and can mount mature T cell-dependent and T cell-independent antibody responses, entailing somatic hypermutation, class-switch recombination, and plasma cell and memory B cell differentiation. Upon flagellin or a Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccination, THX mice mount neutralizing antibody responses to Salmonella or severe acute respiratory syndrome coronavirus 2 Spike S1 receptor-binding domain, with blood incretion of human cytokines, including APRIL, BAFF, TGF-β, IL-4 and IFN-γ, all at physiological levels. These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics."

Mice created with full human immune systems for the first time 

Scientists create first mouse model with complete, functional human immune system (original news release)

A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses (open access)

Fig. 1: THX mice support full and sustained development of human immune cells.