Genetically modified mice

B-NDG knockout mice

NOD.CB17-Prkdc^scid IL2rg^tm1/BcgenHsd

The B-NDG model is a single knockout mouse with an ultra-immunodeficient phenotype. The model was generated by Biocytogen by deleting the IL2rg gene from NOD-scid mice.

Prkdc (protein kinase DNA-activated catalytic) null scid mutation is characterized by significantly deficient of functional T cells and B cells.

The Common gamma chain gene (IL2RG) deletion results in a lack of functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, which results in the lack of functional NK cells.

Characteristics:

Autosomal recessive, single nucleotide polymorphism with Prkdc gene on chromosome 16
Coat: Albino
Common gamma chain gene (II2rg) interrupted
Deficiency in cytokine signaling
Deficient in T and B cells
High humanization capability
Lacks functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21
Lacks NK cells
Severe lymphocyte development impairment

Research Use:

Aging, Chemoresistance, General studies, Immunotherapy, Oncology, Stem cells, Tumor Cell Growth, Tumor growth,

Features and advantages

• Severe Immunodeficiency ➝ Ultra immunodeficient phenotype enhances tumor cell acceptance
• High humanization capability ➝ Minimal rejection of human-derived cells and tissue

Rag2-Il2rg double knockout mice (R2G2®)

B6;129-Rag2^tm1FwaII2rg^tm1Rsky/DwlHsd

The R2G2 model is a double knockout mouse with an ultra immunodeficient phenotype. The model was created by backcrossing the IL2RG (common gamma chain) mutation on to a mixed background mouse (C57BL/6 and129 mix) with a mutation in Rag2. The recombination activating gene 2 (Rag2) interruption causes a deficiency in T and B cells. The Common gamma chain gene (IL2RG) interruption results in a lack of functional receptors for IL-2, IL-4, IL-7, IL-9 and IL-15.

Characteristics

Coat white-bellied, light chinchilla (light tan)
Common gamma chain gene (II2rg) interrupted
Decreased dendritic cells
Decreased macrophage cells
Decreased neutrophils
Deficient in T and B cells
Lacks functional receptors for IL-2, IL-4, IL-7, IL-9 and IL-15
Lacks NK cells
Recombination activating gene 2 (Rag2) interrupted
Severe lymphocyte development impairment

Research Use

Imaging, Immunology, Immunotherapy, Neuropathology, Oncology, Stem cells, Tumor biology, Tumor growth, Cancer cell transplantatio, Infectious disease

B-NDG B2m double knockout plus mice

NOD.CB17-Prkdc^scidIl2rg^tm1B2m^tm1Fcgrt^tm1(B2m)/BcgenHsd

The B-NDG B2m model is a double knockout mouse with an ultra-immunodeficient phenotype. The model was generated by Biocytogen by deleting the IL2rg gene from NOD-scid mice. Prkdc (protein kinase DNA-activated catalytic) null scid mutation is characterized by significantly deficient of functional T cells and B cells.

The Common gamma chain gene (IL2RG) deletion results in a lack of functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, which results in the lack of functional NK cells.

The B2m gene is fused in the FcRn gene while the endogenous murine B2m gene is knocked out. This mouse combines the B-NDG mouse background with the absence of the MHC class I molecule β2m and shows no difference in the metabolism of IgG drugs in mice compared with wild-type mice. This model is effective against GVHD effects.

Characteristics

• Common gamma chain gene (II2rg) interrupted
• Lacks functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21
• Autosomal recessive, single nucleotide polymorphism with Prkdc gene on chromosome 16
• Severe lymphocyte development impairment
• Deficient in T cells
• Deficient in B cells
• Lacks NK cells
• MHC class I deficiency
• Deficiency in cytokine signaling
• High humanization capability

Research use

Oncology research, Cancer cell transplantation, Immunology, Infectious disease, Graft vs. host disease research, Humanization applications

Features and advantages

• Severe Immunodeficiency ➝ Ultra immunodeficient phenotype enhances tumor cell acceptance
• High humanization capability ➝ Minimal rejection of human-derived cells and tissue
• Increased survival and decreased GvHD ➝ Significant extension of survival & remarked delay of onset and reduction of severity of GvHD in human PBMC engrafted B2M/FcRn mice
• Antibody half-life ➝ Improved antibody halflife compared with B2m KO mice

B-NDG hIL15 mice

NOD.CB17-Prkdc^scidIl2rg^tm1Il15^tm1(IL15)/BcgenHsd

The B-NDG hIL15 model is a single knockout mouse with an ultra-immunodeficient phenotype. The model was generated by Biocytogen by deleting the IL2rg gene from NOD-scid mice. Prkdc (protein kinase DNA-activated catalytic) null scid mutation is characterized by significantly deficient of functional T cells and B cells.

The Common gamma chain gene (IL2RG) deletion results in a lack of functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, which results in the lack of functional NK cells.

The human IL15 gene was inserted after the 5′UTR of the mouse IL15, so that this mouse expresses the human IL15 cytokine. This mouse combines a B-NDG mouse background and expresses human IL15 cytokine. It will become a suitable animal model to investigate development and function of human NK cells.

Characteristics

• Common gamma chain gene (II2rg) interrupted
• Lacks functional receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21
• Autosomal recessive, single nucleotide polymorphism with Prkdc gene on chromosome 16
• Severe lymphocyte development impairment
• Deficient in T cells
• Deficient in B cells
• Lacks NK cells
• Deficiency in cytokine signaling
• High humanization capability

Research use

Oncology research, Cancer cell transplantation, Immunology, Infectious disease, NK cell role in tumorigenesis, Antibody drug efficacy evaluation, Humanization applications

Features and advantages

• Severe Immunodeficiency ➝ Ultra immunodeficient phenotype enhances tumor cell acceptance
• Reduced leakiness ➝ Decreased leakiness as compared to SCID models
• High humanization capability ➝ Minimal rejection of human-derived cells and tissue
• Expresses human IL15 cytokine ➝ Ability to investigate the development and function of human NK cells

Humanized ACE2 (hACE2) knockin mice

C57BL/6Hsd-Ace2^em1(ACE2)Env

Angiotensin-converting enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin system (RAS). RAS regulates blood volume and arterial tone, as such, ACE2 is a common target for the treatment of hypertension. ACE2 is highly expressed in several human tissues including the gastrointestinal tract, liver, gallbladder, kidney, urinary bladder, testes, placenta and fallopian tube, with lower expression levels in the lungs and pancreas. It also serves as the primary receptor for cell entry for the SARS-CoV and SARS-CoV-2 viruses. Binding of the coronavirus spike (S) protein to ACE2 initiates fusion of the cell and viral membranes for cell entry. ACE2-S protein binding is the critical initial step for coronavirus infection and is being investigated as a potential coronavirus drug target.

This hACE2 knockin mouse model was generated by integrating a codon optimized human ACE2 cDNA expression cassette into the mouse Ace2 gene through CRISPR-based technology. As a result, the mouse Ace2 gene promoter and other regulatory elements drive expression of the human ACE2 protein while terminating mouse Ace2 gene expression.

Characteristics

• Human ACE2 expression was confirmed by measuring mRNA levels in heterozygous and homozygous females and hemizygous males.
• Background strain: C57BL/6

Research use

Infectious disease, COVID-19, SARS

Humanized Tmprss2 (hTmprss2) knockin mice

C57BL/6Hsd-Tmprss2^{em1(TMPRSS2)Env}

Tmprss2 is a transmembrane serine protease that is involved in viral infection. Both influenza viruses and human coronaviruses, including HCoV-229E, MERS-CoV, SARS-CoV, and SARS-CoV-2, depend on Tmprss2 proteolytically cleaving (i.e., priming) the viral spike glycoprotein, which triggers fusion of the viral envelope and host cell membrane, allowing the virus to enter the cell. Tmprss2 also has a pivotal role in the development and progression of prostate cancer. The fusion of the TMPRSS2 gene with the ERG oncogene is the most frequent genomic alteration in prostate cancer.

The hTmprss2 KI mouse model was generated using CRISPR-based technology to mediate the integration of a codon optimized human TMPRSS2 cDNA expression cassette into the mouse Tmprss2 gene locus. As a result, the mouse Tmprss2 gene promoter and other regulatory elements will drive the human Tmprss2 protein expression whereas the mouse Tmprss2 gene expression will be terminated.

Characteristics

• Background strain: C57BL/6

Research use

Infectious disease, COVID-19, SARS and MERS

Humanized ACE2/Tmprss2 (hACE2/hTmprss2) double knockin mice

C57BL/6Hsd-Ace2^em1(ACE2)EnvTmprss2^{em1(TMPRSS2)Env}

Cellular infection by coronaviruses, including SARS-CoV and SARS-CoV-2, is a two-step process that is utilizes the host proteins ACE2 and Tmprss2. Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system that regulates blood volume and arterial tone, is the entry receptor for SARS-CoV and SARS-CoV-2. The S1 subunit of the coronavirus spike (S) protein contains a receptor binding domain (RBD) that recognizes and binds to ACE2. Upon receptor binding, Tmprss2, a transmembrane serine protease, cleaves the S protein at the junction of the S1 and S2 subunits, allowing fusion of the cellular and viral membranes and the subsequent entry of the coronavirus into the cell. As such, ACE2 and Tmprss2 are being investigated as potential targets for anti-viral drugs.

The hACE2 and hTmprss2 single knockin models were generated by integrating a codon optimized human ACE2 or TMPRSS2 cDNA expression cassette into the respective mouse gene through CRISPR-based technology. This results in the mouse gene promoter and other regulatory elements driving the expression of the human ACE2 or Tmprss2 protein while terminating expression of the respective mouse gene. The hACE2/hTmprss2 double knockin mouse was created through the crossing of the hACE2 and hTmprss2 single knockin mouse models.

Characteristics

• Background strain: C57BL/6

Research use

Infectious disease, COVID-19, SARS and MERS