Supplemental information
NEMO links nuclear factor-B to human diseases
Gunter Maubach, Michael Naumann
Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg
Authors’ affiliation
Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg
Leipziger Str. 44, 39120 Magdeburg,
Germany
Corresponding author:
Michael Naumann
Tel.: +49 391 67 13227
Fax: +49 391 67 13312
Email:
Supplementary Table S1. NEMO in experimental animal models
Target / Genotype / Disease/Phenotype / Ref.Ikbkg / Ikbkgtm1Mak/Y (MGI: 3851597) 129P2/OlaHsd * C57BL/6 / Male embryos die between 12.5 and 13.5 / [1]
Ikbkg / Ikbkgtm1Mpa/Ikbkg+ (MGI: 3844910) Ikbkgtm1Mpa/Y (MGI: 3844909) C57BL/6J / Incontinentia pigmenti in female; embryonic lethal in male / [2]
Ikbkg / Ikbkgtm1Mka/Ikbkg+ (MGI:3621818) Ikbkgtm1Mka/Y (MGI:3621817) 129S1/Sv * 129X1/SvJ * C57BL/6J / Incontinentia pigmenti in female; lethal at E12 in male / [3]
Ikbkg cond. / Ikbkgtm1.1Mpa/Ikbkgtm1.1Mpa (Alfp-Cre) NemoLPC-KO C57BL/6 / Liver parenchymal cell-specific,
hepatocellular carcinoma / [4]
Ikbkg cond. cn8 / Ikbkgtm1.1Mpa/Ikbkgtm1.1MpaTg(Alb1-cre)7Gsc/0 (MGI: 3700375) NemoLPC-KO C57BL/6 * FVB/N / Steatohepatitis and hepatocellular carcinoma / [3]
Ikbkg cond. cn4, 5, 6 / Ikbkgtm1.1Chtr/Ikbkgtm1.1ChtrTg(Alb1-cre)7Gsc/0 (MGI: 4355726) Ikbkgtm1.1Chtr/Y Tg(Alb1-cre)7Gsc/0 (MGI: 4355843) C57BL/6*FVB/N*SJL Ikbkgtm1.1Chtr/Ikbkgtm1.1ChtrTg(Alb1-cre)7Gsc/0 (MGI: 4461040) FVB/N / cellular, hematopoietic, homeostasis, immune, liver/biliary, mortality/aging, neoplasm / [5]
Ikbkg mouse K392R / Ikbkgtm1Dwb/ Ikbkgtm1Dwb (MGI: 3797724)
unspecified / Immune system (blunted cytokine responses to TLR agonists) in female / [6]
Ikbkg mouse L153P / Ikbkgm1Btlr/Ikbkg+ (MGI: 3808878) Ikbkgm1Btlr/Y (MGI: 3808880) C57BL/6J-Ikbkgm1Btlr / Reduced female fertility cellular, hematopoietic, immune, reproductive in male / [7]
Ikbkg human K285R,K399R / Ikbkgtm1.1Dwat/Ikbkg+ (MGI: 5543237) Ikbkgtm1.1Dwat/Y (MGI: 5543238)
B6Cg-Ikbkgtm1.1Dwat / hematopoietic, immune, integument, reproductive in female
embryonic lethal in male / [8]
Ikbkg cond. / NemoIEC-KO intestinal epithelial cells / Chronic intestinal inflammation / [9]
Ikbkg cond. / NemoIEC-KO intestinal epithelial cells
Villin-cretg/WT
C57BL/6 / chronic colitis, diarrhea, thickening of the colonic wall, epithelial erosion and ulcer formation / [10]
Ikbkg cond. / NemoEKO male
NemoEHET heterozygote female
keratinocytes / Skin lesions / [11]
Ikbkg cond. / NemobeKO/Nemofl
Brain endothelial cell specific (Slco1c1-CreERT2) tamoxifen-inducible / Not described used for targeted delivery of therapeutic genes to the CNS / [12, 13]
Abbreviations: 129P2/OlaHsd, C57BL/6, 29S1/Sv, 129X1/SvJ, FVB/N, SJL: different mouse strains; tm1Mak: targeted mutation 1, TakMak; tm1Mpa: targeted mutation 1, ManolisPasparakis; tm1Mka: targeted mutation 1, Michael Karin; tm1.1Mpa: targeted mutation 1.1, ManolisPasparakis; tm1.1Chtr: targeted mutation 1.1, Christian Trautwein; tm1Dwb: targeted mutation 1, Dean Ballard; m1Btlr: mutation 1, Bruce Beutler; tm1.1Dwat: targeted mutation 1.1, Derek W Abbott; LPC-KO: liver parenchymal cell-knockout; Alb1-Cre: Crerecombinase under control of the Albumin promoter; IEC-KO: instestinal epithelial cell-knockout; Villin-Cre: Crerecombinase under control of the villin promoter; EKO: epidermal keratinocyte-knockout; EHET: epidermis of heterozygous females expected to have NEMO-deficient and -expressing cells; beKO: brain endothelial cell-knockout; Slco1c1-CreERT2: tamoxifen inducible Crerecombinase under control of the solute carrier organic anion transporter family member 1C1 promoter
1 Rudolph, D., et al. (2000) Severe liver degeneration and lack of NF-κB activation in NEMO/IKKγ-deficient mice. Genes Dev. 14, 854-862
2 Makris, C., et al. (2000) Female mice heterozygous for IKKg/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell 5, 969-979
3 Schmidt-Supprian, M., et al. (2000) NEMO/IKKg-deficient mice model incontinentia pigmenti. Mol. Cell 5, 981-992
4 Luedde, T., et al. (2007) Deletion of NEMO/IKKg in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11, 119-132
5 Beraza, N., et al. (2009) Hepatocyte-specific NEMO deletion promotes NK/NKT cell– and TRAIL-dependent liver damage. J. Exp. Med. 206, 1727-1737
6 Ni, C.-Y., et al. (2008) Cutting Edge: K63-Linked Polyubiquitination of NEMO Modulates TLR Signaling and Inflammation In Vivo. J. Immunol. 180, 7107-7111
7 Siggs, O.M., et al. (2010) A mutation of Ikbkg causes immune deficiency without impairing degradation of IκBα. Proc. Natl. Acad. Sci. U. S. A. 107, 3046-3051
8 Jun, JaniceC., et al. (2013) Innate Immune-Directed NF-κB Signaling Requires Site-Specific NEMO Ubiquitination. Cell Rep. 4, 352-361
9 Nenci, A., et al. (2007) Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557-561
10 Vlantis, K., et al. (2016) NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions. Immunity 44, 553-567
11 Nenci, A., et al. (2006) Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling. Hum. Mol. Genet. 15, 531-542
12 Körbelin, J., et al. (2016) A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases. EMBO Mol. Med. 8, 609-625
13 Ridder, D.A., et al. (2015) Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J. Exp. Med. 212, 1529-1549