A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
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Petr Kasparek
Abstract
Netherton syndrome (NS) is caused by mutations in the SPINK5 gene. Several Spink5-deficient mouse models were generated to understand the mechanisms of NS in vivo. However, Spink5-deficiency in mice is associated with postnatal lethality that hampers further analysis. Here we present a viable mouse model for NS generated by mosaic inactivation of the Spink5 gene. We propose that these mice are a valuable experimental tool to study NS, especially for long-term studies evaluating potential therapeutic compounds. Furthermore, we show that mosaic inactivation of a gene using TALENs or CRISPR/Cas9 systems can be used to study lethal phenotypes in adult mice.
Acknowledgments
We are grateful to Nicole Chambers for proofreading the article and to Attila Juhasz, Sandra Potysova, Irena Placerova, Veronika Libova, and Henrieta Palesova for excellent technical assistance. Financial support was given to R.S. by MEYS, (NPU II project LQ1604).
Conflict of interest statement: The authors declare that no conflict of interest exists.
Funding: Academy of Sciences of the Czech Republic (Grant/Award number: ‘RVO 68378050‘). MEYS (Grant/Award number: ‘CZ.1.05/1.1.00/02.0109’, ‘LM2011032’).
References
Bitoun, E., Micheloni, A., Lamant, L., Bonnart, C., Tartaglia-Polcini, A., Cobbold, C., Al Saati, T., Mariotti, F., Mazereeuw-Hautier, J., Boralevi, F., et al. (2003). LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. Hum. Mol. Genet. 12, 2417–2430.10.1093/hmg/ddg247Suche in Google Scholar PubMed
Bonnart, C., Deraison, C., Lacroix, M., Uchida, Y., Besson, C., Robin, A., Briot, A., Gonthier, M., Lamant, L., Dubus, P., et al. (2010). Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. J. Clin. Invest. 120, 871–882.10.1172/JCI41440Suche in Google Scholar PubMed PubMed Central
Briot, A., Deraison, C., Lacroix, M., Bonnart, C., Robin, A., Besson, C., Dubus, P., and Hovnanian, A. (2009). Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J. Exp. Med. 206, 1135–1147.10.1084/jem.20082242Suche in Google Scholar PubMed PubMed Central
Crosby, J.R., Seifert, R.A., Soriano, P., and Bowen-Pope, D.F. (1998). Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Nat. Genet. 18, 385–388.10.1038/ng0498-385Suche in Google Scholar PubMed
Descargues, P., Deraison, C., Bonnart, C., Kreft, M., Kishibe, M., Ishida-Yamamoto, A., Elias, P., Barrandon, Y., Zambruno, G., Sonnenberg, A., et al. (2005). Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity. Nat. Genet. 37, 56–65.10.1038/ng1493Suche in Google Scholar PubMed
Descargues, P., Deraison, C., Prost, C., Fraitag, S., Mazereeuw-Hautier, J., D’Alessio, M., Ishida-Yamamoto, A., Bodemer, C., Zambruno, G., and Hovnanian, A. (2006). Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. J. Invest. Dermatol. 126, 1622–1632.10.1038/sj.jid.5700284Suche in Google Scholar PubMed
Diociaiuti, A., Castiglia, D., Fortugno, P., Bartuli, A., Pascucci, M., Zambruno, G., and El Hachem, M. (2013). Lethal Netherton syndrome due to homozygous p.Arg371X mutation in SPINK5. Pediatr. Dermatol. 30, e65–e67.10.1111/pde.12076Suche in Google Scholar PubMed
Hewett, D.R., Simons, A.L., Mangan, N.E., Jolin, H.E., Green, S.M., Fallon, P.G., and McKenzie, A.N. (2005). Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. Hum. Mol. Genet. 14, 335–346.10.1093/hmg/ddi030Suche in Google Scholar PubMed
Hsu, P.D., Lander, E.S., and Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262–1278.10.1016/j.cell.2014.05.010Suche in Google Scholar PubMed PubMed Central
Huijbers, I.J., Krimpenfort, P., Berns, A., and Jonkers, J. (2011). Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse models. Bioessays 33, 701–710.10.1002/bies.201100018Suche in Google Scholar PubMed PubMed Central
Chavanas, S., Bodemer, C., Rochat, A., Hamel-Teillac, D., Ali, M., Irvine, A.D., Bonafe, J.L., Wilkinson, J., Taieb, A., Barrandon, Y., et al. (2000). Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat. Genet. 25, 141–142.10.1038/75977Suche in Google Scholar PubMed
Kasparek, P., Krausova, M., Haneckova, R., Kriz, V., Zbodakova, O., Korinek, V., and Sedlacek, R. (2014). Efficient gene targeting of the Rosa26 locus in mouse zygotes using TALE nucleases. FEBS Lett. 588, 3982–3988.10.1016/j.febslet.2014.09.014Suche in Google Scholar PubMed
Sales, K.U., Masedunskas, A., Bey, A.L., Rasmussen, A.L., Weigert, R., List, K., Szabo, R., Overbeek, P.A., and Bugge, T.H. (2010). Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat. Genet. 42, 676–683.10.1038/ng.629Suche in Google Scholar PubMed PubMed Central
Shirane, M., Sawa, H., Kobayashi, Y., Nakano, T., Kitajima, K., Shinkai, Y., Nagashima, K., and Negishi, I. (2001). Deficiency of phospholipase C-γ1 impairs renal development and hematopoiesis. Development 128, 5173–5180.10.1242/dev.128.24.5173Suche in Google Scholar PubMed
Sun, J.D. and Linden, K.G. (2006). Netherton syndrome: a case report and review of the literature. Int. J. Dermatol. 45, 693–697.10.1111/j.1365-4632.2005.02637.xSuche in Google Scholar PubMed
Yang, T., Liang, D., Koch, P.J., Hohl, D., Kheradmand, F., and Overbeek, P.A. (2004). Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice. Genes. Dev. 18, 2354–2358.10.1101/gad.1232104Suche in Google Scholar PubMed PubMed Central
Yen, S.T., Zhang, M., Deng, J.M., Usman, S.J., Smith, C.N., Parker-Thornburg, J., Swinton, P.G., Martin, J.F., and Behringer, R.R. (2014). Somatic mosaicism and allele complexity induced by CRISPR/Cas9 RNA injections in mouse zygotes. Dev. Biol. 393, 3–9.10.1016/j.ydbio.2014.06.017Suche in Google Scholar PubMed PubMed Central
Supplemental Material:
The online version of this article (DOI: 10.1515/hsz-2016-0194) offers supplementary material, available to authorized users.
©2016 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: remodelling the KLK landscape down under
- HIGHLIGHT: 6TH INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications
- Mechanistic insight from murine models of Netherton syndrome
- Development of molecules stimulating the activity of KLK3 – an update
- Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors
- Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10
- Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
- A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
- Therapeutic modulation of tissue kallikrein expression
- In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B
- A computational analysis of the genetic and transcript diversity at the kallikrein locus
- Reviews
- Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
- The power, pitfalls and potential of the nanodisc system for NMR-based studies
- Research Articles/Short Communications
- Cell Biology and Signaling
- Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1β and 5-azacytidine
Artikel in diesem Heft
- Frontmatter
- Guest Editorial
- Highlight: remodelling the KLK landscape down under
- HIGHLIGHT: 6TH INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
- Kallikrein(K1)-kinin-kininase (ACE) and end-organ damage in ischemia and diabetes: therapeutic implications
- Mechanistic insight from murine models of Netherton syndrome
- Development of molecules stimulating the activity of KLK3 – an update
- Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors
- Structural basis for the Zn2+ inhibition of the zymogen-like kallikrein-related peptidase 10
- Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis
- A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene
- Therapeutic modulation of tissue kallikrein expression
- In vitro evidence that KLK14 regulates the components of the HGF/Met axis, pro-HGF and HGF-activator inhibitor 1A and 1B
- A computational analysis of the genetic and transcript diversity at the kallikrein locus
- Reviews
- Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome
- The power, pitfalls and potential of the nanodisc system for NMR-based studies
- Research Articles/Short Communications
- Cell Biology and Signaling
- Synergistic induction of cardiomyocyte differentiation from human bone marrow mesenchymal stem cells by interleukin 1β and 5-azacytidine
