Pathways to Discovery: Autoimmune Diseases

To assist researchers in investigating molecular commonalities among different autoimmune diseases, in silico data mining and pathway software were used to integrate the gene/pathway interactions between inflammatory bowel disease (IBD), rheumatoid arthritis, asthma, multiple sclerosis (MS), and psoriasis.

This new, comprehensive resource facilitates the identification of novel therapeutic targets, or the exploration of alternate therapeutic areas for existing targets, by providing the following:

  • Schematics of gene/pathway associations common to IBD, arthritis, asthma, MS, and psoriasis
  • Descriptions of JAX® In Vivo Services for autoimmune disease research
  • Over 100 JAX® Mice strains linked to multiple autoimmune diseases
  • Gene- and disease-specific references
pathways diagram showing autoimmune-disease specific genes
Common genetic pathway interactions exist between different autoimmune diseases. The Jackson Laboratory acknowledges Ingenuity Systems, Inc. for the biological pathway diagram and supporting content. Genes were included if they were associated with two or more disease areas. Enlarge diagram

JAX® In Vivo Services for Autoimmune Disease Research

We provide fully customizable target validation and efficacy testing services with access to the world's largest collection of specialized mouse models of autoimmune disease. Newly available models and customized protocols supplement our standard services to provide an individualized experience. Our study directors and research scientists bring their expertise and collective knowledge of mouse physiology and genetics to work for you.

Inducible models for autoimmune diseases

In addition to the mutant JAX® Mice strains listed throughout this resource, the table below offers an overview of 10 popular autoimmune disease-susceptible strains. These inducible mouse models recapitulate many aspects of the human disease and generally have a short latency to disease onset.

JAX® Mice distributes the best characterized, most genetically-stable mouse strains from both our East Coast, Bar Harbor, ME facility and our new, state-of-the-art West Coast, Sacramento, CA facility. The use of our common inbred strains supports the collection, preservation, and distribution of specialty mutant mouse models for the study of human diseases.

IBD

Stock No. Strain Name Disease development Reference
000664 C57BL/6J  inducible (DSS) Mahler et al. 1998
000651 BALB/cJ inducible (TNBS) Blumberg et al. 1999
001976 NOD/ShiLtJ inducible (DSS) Mahler et al. 1998
004326 C3Bir.129P2(B6)-Il10tm1Cgn/Lt spontaneous (flora-dependent) Kuhn et al. 1993

Rheumatoid arthritis

Stock No. Strain Name Disease development Reference
000670 DBA/1J inducible (collagen) Malfait et al. 2001
000651 BALB/cJ inducible (collagen-antibody) Lange et al. 2005
000653 BUB/BnJ inducible (collagen) Haqqi et al. 1995

Asthma

Stock No. Strain Name Disease development Reference
000651 BALB/cJ  inducible (OVA) Beigelman et al. 2009

Multiple sclerosis

Stock No. Strain Name Disease development Reference
000686 SJL/J inducible (proteolipid protein) Duzhak et al. 2003
001026 BALB/cByJ  inducible Teuscher et al. 1987
100008 NZBWF1/J inducible (MBP) Zamvil et al. 1994
000457 B10.RIII-H2r H2-T18b/(71NS)SnJ inducible (MBP) Zhao et al. 1993

Psoriasis

Stock No. Strain Name Disease development Reference
001803 CBySmn.CB17-Prkdcscid/J inducible (adoptive T cell transfer) Davenport et al. 2002

JAX® Mice

We distribute more than 4,500 mouse models of disease, including the most commonly used, well-characterized inbred mouse strains, such as C57BL/6J (000664), FVB/NJ (001800), DBA/2J (000671), and BALB/cJ (000651). These commonly used strains are available on demand in large quantities (hundreds or thousands) from both our East and West Coast facilities, and their use supports the collection, preservation, and distribution of the thousands of specialty mutant JAX® Mice strains to the research community.

Gene Therapeutic disease areas Gene/protein function and details
Ccl2 Asthma, Multiple Sclerosis, Rheumatoid Arthritis Small cytokine belonging to the CC chemokine family; also known as monocyte chemotactic protein-1 (MCP-1). Recruits monocytes, memory T cells, and dendritic cells to sites of tissue injury and infection.
Cd4 IBD, Psoriasis, Rheumatoid Arthritis Glycoprotein expressed on the surface of helper T lymphocytes and other immune cells. CD4 functions to initiate or augment the early phase of T cell activation.
Cd40 IBD, Multiple Sclerosis, Rheumatoid Arthritis A costimulatory protein found on antigen presenting cells and is required for their activation
Cd40lg IBD, Rheumatoid Arthritis Protein expressed on both CD4+ and CD8+ T cells that aids in stimulating B cells in the immune response.
Cd80 Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Cd80 encodes B7-1, which provides a costimulatory signal necessary for T cell activation and survival. Expressed on a variety of hematopoietic cell types. Also known as Ly53 and CD28LG.
Cd86 Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Cd86 encodes B7-2, which provides a costimulatory signal necessary for T cell activation and survival. Expressed on a variety of hematopoietic cell types. Also known as Ly58 and CD28LG2.
Ciita Multiple Sclerosis, Rheumatoid Arthritis Positive regulator of Class II major histocompatibility complex (MHC) gene transcription. Considered the "master control factor", needed for expression of MHC Class II genes.
Fas IBD, Multiple Sclerosis, Psoriasis TNF-receptor superfamily, death domain containing member. Plays a central role in the physiological regulation of programmed cell death and has been implicated in the pathogenesis of diseases of the immune system. Also known as CD95 and TNFR6.
H2-Eb1 Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis No data is available as there are no relevant JAX® Mice strains at this time.
Ifng Asthma, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Cytokine critical for innate and adaptive immunity. Aberrant expression is associated with a number of autoinflammatory and autoimmune diseases.
Il2ra Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis The interleukin 2 receptor alpha (IL2RA), beta (IL2RB), and the common gamma chain (IL2RG) constitute the high-affinity IL2 receptor, expressed on immune cells, such as lymphocytes. Also known as Ly43 and CD25.
Il4 Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Cytokine that induces differentiation of naive helper T cells. A key regulator of adaptive immunity.
Il6  IBD, Rheumatoid Arthritis An interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine.
Il7 IBD, Multiple Sclerosis, Rheumatoid Arthritis Cytokine important for B and T cell development. Plays an essential role in lymphoid cell survival.
Il10 Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis An anti-inflammatory cytokine primarily produced by monocytes, which has pleiotrophic effects in immunoregulation and inflammation.
Il12a IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Cytokine which has a number of biological activities including T cell-independent induction of interferon (IFN)-gamma. Important for the differentiation of both Th1 and Th2 cells.
Il12b Asthma, IBD, Psoriasis, Rheumatoid Arthritis IL12 p40 subunit. Cytokine expressed by activated macrophages and important for Th1 cell development, regulation and memory.
Il13 Asthma, IBD, Rheumatoid Arthritis No data is available as there are no relevant JAX® Mice strains at this time.
Il23a IBD, Psoriasis No data is available as there are no relevant JAX® Mice strains at this time.
Il1rn IBD, Rheumatoid Arthritis This protein inhibits the activity of interleukin 1 alpha (IL1A) and beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses.
Myd88 Asthma, IBD, Multiple Sclerosis, Rheumatoid Arthritis Adapter protein involved in Toll-like receptor and interleukin 1 receptor signaling pathways within the innate immune response. Activates the transcription factor NF-kappa-B.
Nos2 Asthma, IBD, Multiple Sclerosis Encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines.
Rela IBD, Psoriasis NF-kappa-B or p65 is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis.
Nr3c1 Asthma , IBD, Multiple Sclerosis, Rheumatoid Arthritis No data is available as there are no relevant JAX® Mice strains at this time.
Pomc Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage. Gives rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation.
Pparg Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors, which regulate transcription of various genes. Implicated in the pathology of numerous diseases.
Ptgs2 IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Participates in synthesizing prostanoids involved in pain and inflammation. Also known as cyclooxygenase-2 (COX2).
Tlr2 Asthma, IBD, Multiple Sclerosis, Rheumatoid Arthritis Surface receptor present on multiple immune cells. Binds diverse pathogenic substances and initiates innate immune responses. Also known as CD282 and Ly105.
Tlr4 Asthma, IBD, Multiple Sclerosis, Rheumatoid Arthritis Surface receptor for lipopolysaccharides from Gram-negative bacteria. Receptor engagement initiates innate immune response.
Tnf Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Pleiotropic cytokine promoting inflammation, cell death, proliferation and other responses. Synthesized by many cell types.
Vdr Asthma, IBD, Multiple Sclerosis, Psoriasis, Rheumatoid Arthritis Nuclear receptor capable of transactivating vitamin-D responsive genes.
Multiple Sclerosis Psoriasis Asthma Inflammatory Bowel Disease Rheumatoid Arthritis Ingenuity Systems website

Continue to pathways for inflammatory bowel disease

Diagram key
yellow rounded rectangle therapeutic disease area
grey line gene/pathway associations
blue line with endpoint highlighted gene/pathway associations
blue rectangle symbol transmembrane receptor
grey oval symbol transcription regulator
yellow circle symbol nuclear receptor
green hexagon symbol cytokine
orange diamond symbol enzyme
purple rectangle symbol other