Ifna Complex/Cluster/Region Detail

Summary

• Symbol
  Ifna
• Name
  interferon alpha complex region
• Synonyms
  Ifa

• Feature Type
  complex/cluster/region
• IDs
  MGI:107670
  NCBI Gene: 111654
• Cluster Members
  Ifna14, Ifna-ps1, Ifna9 ... (14 members)
• Candidate for QTL
  1 QTL

Location &
Maps

• Sequence Map
  Genome coordinates not available from the current reference assembly.

• Genetic Map
  Chromosome 4, cytoband C3-C6
• Mapping Data
  85 experiments

Strain
Comparison

• PCR
  2
• RFLP
  20

Expression

• Literature Summary
  1

Sequences &
Gene Models

• NCBI Gene
  111654

Molecular
Reagents

• All nucleic 26

  Genomic 19

  cDNA 3

  Primer pair 2

  Other 2

Other
Accession IDs

MGD-MRK-11200, MGD-MRK-36245

References

• Summaries
  All 181

  Developmental Gene Expression 1
• Earliest
  J:30761 Hanson B, et al., Interferon-mediated natural resistance of mice to arbo B virus infection. Microbios. 1969;1B:51-68
• Latest
  J:361606 Wei W, et al., Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival. J Clin Invest. 2025 Feb 3;135(3)

Ifna Cluster contains:

More Data for these features

Member	Feature Type	Location
Ifna14, interferon alpha 14	protein coding gene	Chr4:88489466-88490035 (-)
Ifna-ps1, interferon alpha gene, pseudogene 1	pseudogene	Chr4:88497124-88498810 (-)
Ifna9, interferon alpha 9	protein coding gene	Chr4:88510050-88510622 (-)
Ifna12, interferon alpha 12	protein coding gene	Chr4:88520817-88521613 (-)
Ifna13, interferon alpha 13	protein coding gene	Chr4:88561878-88562696 (-)
Ifna2, interferon alpha 2	protein coding gene	Chr4:88601444-88602016 (-)
Ifnab, interferon alpha B	protein coding gene	Chr4:88608836-88609505 (-)
Ifna7, interferon alpha 7	protein coding gene	Chr4:88734465-88735037 (+)
Ifna11, interferon alpha 11	protein coding gene	Chr4:88738196-88738768 (+)
Ifna6, interferon alpha 6	protein coding gene	Chr4:88745653-88746222 (+)
Ifna5, interferon alpha 5	protein coding gene	Chr4:88753762-88754331 (+)
Ifna4, interferon alpha 4	protein coding gene	Chr4:88760098-88760658 (+)
Ifna1, interferon alpha 1	protein coding gene	Chr4:88768324-88768893 (+)
Ifna10, interferon alpha 10	unclassified gene	Chr4, Syntenic

Ifna is Candidate Gene for:

QTL	Genetic Location*	Genome Location (GRCm39)	Reference	QTL Note
Bbaa1	Chr4, 43.30 cM	Chr4:55250930-55251078	J:243935	Previous studies revealed a major, differential contribution of Type I IFN to the development of Lyme arthritis in C3H mice, which could be overcome by blocking the Type I IFN receptor signaling with neutralizing mAb or by gene ablation (19, 20). It was noted that Bbaa1, a QTL controlling the severity of Lyme arthritis on Chr4 encompassed a cluster of 15 Type I IFN genes, prompting a more mechanistic analysis of the role of Bbaa1 as a regulator of Lyme arthritis severity (30, 32). In the current study the analysis of QTL Bbaa1 on Chromosome 4 was extended and the type I IFN gene cluster was identified as positional candidates for Bbaa1. Two mouse strains, C57BL/6 and C3H/He, display extremes of arthritis severity and have been used extensively as experimental models for study of disease. Reciprocal interval specific congenic lines (ISCL) were developed between C3H/HeNCrl (C3H) and C57BL/6Ncr (B6) mice to assess the contribution of Bbaa1 to Lyme arthritis and RA, and the dependence on production of type I IFN. Reciprocal ISCL for Bbaa1 on Chr 4 were generated and indicated as B6.C3-Bbaa1(9.32-94.96) Mbp and C3.B6-Bbaa1(3.58-150.8) Mbp. B6, C3H, B6.C3-Bbaa1 and C3.B6-Bbaa1 mice were infected with 2 x 10<4> B. burgdorferi (strain N40) and arthritis was assessed at 4 weeks post infection. Ankle measurements were obtained using a metric caliper before and at 4 weeks of infection. IFNAR1 blocking mAb MAR1-5A3 or isotope control (Bio-XCell) was administered by a single injection the day before infection with B. burgdorferi or the administration of K/BxN serum. (K/BxN serum was collected from KRN/NOD offspring at the peak of spontaneous arthritis (9 weeks)). K/BxN serum was administered by injection on days 0 and 2. Gene expression of joint tissue was examined in the tibiotarsal joints. Bone marrow-derived macrophages (BMDMs) were isolated from the femurs and tibias. Statistical analysis was performed using Prism 5.0c software. Statistical significance (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). Experimental results demonstrated that Bbaa1 regulates arthritis severity on the B6 background, [Fig 1]. More severe ankle swelling and arthritic lesions were seen in the infected B6.C3-Bbaa1 mice than in the parental B6 mice. Although the B6.C3-Bbaa1 congenic interval was large (9.32-94.97 Mbp) and encoded numerous genes, it nevertheless encompassed the IFN/cluster (88.5-88.7 Mbp) that encode Type I IFNs implicated in Lyme arthritis. All IFN and IFN proteins signal through the IFNAR receptor, comprised of IFNAR1 and IFNAR2 chains. To determine if the greater arthritis in B6.C3-Bbaa1 mice relative to B6 mice was dependent on Type I IFN, B6.C3-Bbaa1 mice were treated with a blocking mAb to IFNAR1 component of the Type I IFN receptor (MAR1-5A3) one day prior to infection. B6.C3-Bbaa1 mice treated with isotype control mAb developed more severe Lyme arthritis than B6 mice as assessed by ankle measurement and lesion scoring [Fig. 2], similar to the results of Fig. 1. Administration of the receptor blocking mAb reduced arthritis severity to levels indistinguishable from wild type B6. Thus, the increased arthritis severity of B6.C3- Bbaa1 mice was a function of Type I IFN responses dependent on feed forward amplification through the IFNAR1 receptor, and identified the IFN cluster as a positional candidate for Bbaa1. Type I IFNs have also been identified in patients with various manifestations of Lyme disease, including skin lesions and cognitive deficits, and have been implicated in in B lymphocyte accumulation in the lymph nodes of infected mice.

*cM position of peak correlated region/marker