Mouse Models

At NCARD we utilise a variety of pre-clinical models to better understand the dynamics of host-tumour and tumour-treatment interactions. Some of the models we have available are listed below. Original references or links to vendor information are supplied where available.

Inbred mouse strains: Common laboratory inbred mouse strains such as BALB/c and C57Bl6/J form the backbone of much of our pre-clinical work.

• BALB/cJ : a commonly used inbred mouse stain. JAX stock No# 000651
• C57BL/6J is the most widely used inbred strain and the first to have its genome sequenced. JAX stock No 000664#

Transgenic mouse strains:

• BALB/c Foxp3.dtr.Crslc: BALB/c based mouse model in which the administration of diphtheria toxin (DT) leads to specific depletion of regulatory T cells (Treg) due to expression of DT receptor-enhanced GFP under the control of the Foxp3 promoter. (PMID: 19923467). Mice are maintained in house.
• MexTAg mice: Asbestos induced mesothelioma mouse model in which expression of the Simian Virus 40 large T antigen (SV40 TAg) is controlled by mesothelin tissue‑specific promoter. TAg phenocopies loss of the tumour suppressor gene p16 and thus MexTAg mice reliably develop mesothelioma, but only after asbestos exposure (PubMed Refs 17108115, 20850297, 26680231). These mice form the basis of the MexTAg research program. Mice are maintained in house.

TCR transgenic strains:

• BABL/c CL4: CD8 TCR transgenic mouse whose CD8 T cells predominantly recognise the MHC class I (H-2K^d) restricted CL4 epitope of PR8 influenza HA protein. (PMID: 8757600)
• BALB/c HNT: CD4 TCR transgenic mouse whose CD4 T cells predominantly recognise the MHC class II (I‑A^d)‑restricted TCR specific for the PR8 influenza HA peptide 126–138 (HNTngvtaacshe) (PMID: 7889402).

TCR congenic strains:

• BALB/c CL4 x Thy1.1: Congenic BALB/c CL4 strain expressing C57Bl/6 Thy 1.1 allele. The T-cell receptor expressed from this transgene is specific for influenza virus A/PR/8 hemagglutinin in the context of the MHC class I molecule H2-K^d. The Thy1.1 allele serves as a marker for following donor CD8+ T cells in vitro. Cell populations derived from these transgenic mice can be distinguished from syngeneic host and other mice with the alternate allele via flow cytometry. JAX stock No# 005307. Mice are maintained in house.
• BALB/c HNT x Thy1.1: Congenic BALB/c HNT strain expressing C57Bl/6 Thy 1.1 allele. The T‑cell receptor expressed from this transgene is specific for influenza virus A/PR/8 hemagglutinin HNT peptide 126–138 (HNTngvtaacshe), in the context of the MHC class II molecule I‑A^d. The Thy1.1 allele serves as a marker for following donor CD8+ T cells in vitro. Cell populations derived from these transgenic mice can be distinguished from syngeneic host and other mice with the alternate allele via flow cytometry. Mice are maintained in house.

Immunodeficient mice

NCARD uses a variety of immunodeficient mice, which are mostly sourced from commercial vendors. Immunodeficient mouse strains are invaluable when assessing the role of immune cell subsets in anti‑tumour immunity.

• BALB/c nude mice: A spontaneous mutation in Foxn1^nu induces abnormal hair growth (nude phenotype). Nude mice are athymic (lack a thymus); homozygous nude mice lack T cells and suffer from a lack of cell-mediated immunity.– JAX stock No# 002019
• B6 RAG-1^-/-: Mice homozygous for the Rag1^tm1Mom mutation produce no mature T cells or B cells. – JAX stock No# 002216 or C57BL/6J isogenic Rag1 knock-out strain is also available as Stock No. 034159.
• NOD^scid: Mice homozygous for the severe combined immune deficiency spontaneous mutation Prkdcscid, commonly referred to as scid, are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironmentsevere combined immune deficient phenotype on Non obese diabetic genetic background. (JAX stock No# 001303).
• BALB^scid: These animals carry the severe combined immune deficiency mutation (scid) on the BALB/c background. JAX stock No# 001803.
• NOD scid Gamma (NSG^-/-): These mice carry two mutations on the NOD/ShiLtJ genetic background; severe combined immune deficiency (scid) and a complete null allele of the IL2 receptor common gamma chain (IL2rgnull). JAX stock No# 005557