Pathways to Discovery: Autoimmune Diseases

This comprehensive tool will save you the time and headache of determining molecular commonalities among different autoimmune diseases. You'll find actionable information on gene/pathway interactions between inflammatory bowel disease (IBD), rheumatoid arthritis, asthma, multiple sclerosis (MS) and psoriasis. The Pathways resource is also an invaluable time-saving device for non-autoimmune researchers as these same genes play important roles in cancer, Alzheimer's, atherosclerosis and obesity. In silico data mining and pathway software were used to integrate the interactions between diseases and bring the resource to life.

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
  • 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

Inducible models for autoimmune diseases

In addition to the mutant JAX® Mice strains listed throughout this resource, the table below offers an overview of more than a dozen 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, Calif. 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

 
Helper T Cell Profile in Mouse Models of Autoimmune Disease

Helper T cells are lymphocytes capable of activating and directing a variety of immune cells to generate a successful immune response to infection. Three major subgroups of Th cells have been defined, Th1, Th2, and Th17, each with distinct cytokine products and biological functions*. Understanding the Th cell subgroup involved in autoimmune disease pathogenesis may lead to the development of novel treatments or identification of better models for efficacy testing current therapies for common autoimmune diseases. This resource lists the Th cell subset(s) linked to each specific mouse model, the particular cytokines secreted by each Th cell subgroup, and supporting references.

  Helper Cell Subset*
Disease Area Model Mouse Strain Th1 Th2 Th17
Inflammatory Bowel Disease DSS-induced (acute) C57BL/6J (000664) or BALB/cJ (000651) - - -
DSS-induced (chronic) C57BL/6J (000664)

-

+
Alex et al. 2009

-

  TNBS-induced BALB/cJ (000651) +
Neurath et al. 1995
- +
Daniel et al. 2008
Adoptive CD4+CD45RBhi
T cell transfer
CBySmn.CB17-Prkdcscid/J (001803) +
Ogino et al. 2011
+
Kanai et al. 2006
+
Kulberg et al. 2006
Rheumatoid Arthritis Collagen antibody-induced BALB/cJ (000651) - - -
  Collagen-induced DBA/1J (000670) DBA/1LacJ (001140) +
Malfait et al. 1998
- +
Lubberts et al. 2004
Asthma OVA-induced BALB/cJ (000651) - +
Webb et al. 2000
+
Hellings et al. 2003
Multiple Sclerosis PLP-EAE
MOG-EAE
SJL/J (000686)
C57BL/6J (000664)
+
Mohindru et al. 2004
- +
O'Connor et al. 2008
Psoriasis CD4+CD45RBhi Adoptive T cell transfer CBySmn.CB17-Prkdcscid/J (001803) +
Hong et al. 2011
- +
Ma et al. 2008

* Th1: Initiating Cytokine IL-12; Effector Cytokines INFγ, IL-2, TNFβ
   Th2: Initiating Cytokine IL-4 Effector Cytokines IL-5, IL-4, IL-13, IL-6
   Th17: Initiating Cytokine IL-21, TNFβ, IL-6 Effector Cytokines IL-17, IL-22, IL-26

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