Humanized Immune System Mouse Models

NKG mice carry the Prkdc scid mutation, which impairs T- and B-cell development, together with an Il2rg knockout, which severely disrupts NK-cell development. Cyagen regularly monitors colony genetics, immune function, health, and breeding performance to maintain model quality.

NKG mice support efficient tumor engraftment, high tumor burden, and relatively long survival in many xenograft models.

In one THP-1 intravenous model, Cyagen NKG mice showed detectable tumor burden by Day 3 and survived for 33 days, compared with 14 days for a comparator strain.

Because growth rates vary by cell line, a pilot study is recommended to confirm engraftment, tumor growth, and the appropriate experimental timeline. For PBMC-humanized models, the interval between PBMC and tumor-cell transplantation should also be optimized.

Cyagen’s optimized neonatal HSC reconstitution process offers:
·High post-irradiation survival
·Reliable intravenous injection
·High reconstitution success
·More animals generated from a single donor
·Broader reconstitution of human immune-cell subtypes
HSC reconstitution requires sublethal irradiation, a longer development period, and higher costs. It is best suited to studies involving multiple immune-cell populations or complex antitumor mechanisms.

PBMC Model (High GvHD Risk): Transplanted adult human Peripheral Blood Mononuclear Cells contain mature, fully differentiated human T cells. These T cells recognize mouse major histocompatibility complex (MHC) molecules as foreign antigens, triggering a severe immune attack against host tissues (causing weight loss, hunched posture, hair loss, skin lesions, and diarrhea). This severe reactivity restricts the experimental window to a short period (typically 2–4 weeks).
HSC Model (Low GvHD Risk): Human Hematopoietic Stem Cells ($CD34^+$ HSCs) differentiate into immune cells in situ inside the host mouse. During T-cell development in the host thymus, emerging human T cells undergo central tolerance (negative selection) against mouse antigens. Because autoreactive cells against host tissues are largely deleted, HSC-humanized mice acquire self-tolerance to the host, resulting in a significantly lower incidence of GvHD and a much longer experimental window (often 6+ months).

Common approaches include:

HSC transplantation: Human CD34+ hematopoietic stem cells generate multiple immune-cell lineages.
PBMC transplantation: Mature human immune cells provide rapid, short-term immune reconstitution.
Human thymus transplantation: Supports human T-cell development, often together with HSC transplantation.
Spleen or lymph-node transplantation: Provides additional human immune-cell development and functional support.

Spontaneous tumors are rare, although isolated cases of lymphoma may occur.
NKG mice do not typically develop spontaneous type 1 diabetes because they lack functional T and B cells capable of attacking pancreatic beta cells. However, metabolic abnormalities resembling type 2 diabetes may develop under specific experimental conditions, such as a high-fat diet.