Abstract
Heritable skin diseases represent a broad spectrum of clinical manifestations due to mutations in ∼500 different genes. A number of model systems have been developed to advance our understanding of the pathomechanisms of genodermatoses. Zebrafish (Danio rerio), a freshwater vertebrate, has a well-characterized genome, the expression of which can be easily manipulated. The larvae develop rapidly, with all major organs having largely developed by 5–6 days post-fertilization, including the skin which consists at that stage of the epidermis comprising two cell layers and separated from the dermal collagenous matrix by a basement membrane zone. Here, we describe the use of morpholino-based antisense oligonucleotides to knockdown the expression of specific genes in zebrafish and to examine the consequent knockdown efficiency and skin phenotypes. Zebrafish can provide a useful model system to study heritable skin diseases.
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References
Lieschke G, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nature Rev Genet 8:353–367
Li Q, Uitto J (2010) The mineralization phenotype in Abcc6−/− mice is affected by Ggcx gene deficiency and genetic background—a model for pseudoxanthoma elasticum. J Mol Med 88:173–181
Hovnanian A (2010) Modifier genes in pseudoxanthoma elasticum: novel insights from the Ggcx mouse model. J Mol Med 88:149–153
Li CF, MacDonald JR, Wei RY, Ray J, Lau K, Kandel C, Koffman R, Bell S, Scherer SW, Alman BA (2007) Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse. BMC Genomics 8:92
Sprecher E (2010) Familial tumoral calcinosis: from characterization of a rare phenotype to the pathogenesis of ectopic calcification. J Invest Dermatol 130:652–660
Vanchieri C (2001) Move over, mouse: make way for the woodchucks, ferrets, and zebrafish. J Natl Cancer Inst 93:418–419
Li Q, Frank M, Thisse C, Thisse B, Uitto J (2011) Zebrafish: a model system to study heritable skin diseases. J Invest Dermatol 131:565–571
Le GD, Morvan-Dubois G, Sire JY (2004) Skin development in bony fish with particular emphasis on collagen deposition in the dermis of the zebrafish (Danio rerio). Int J Dev Biol 48:217–231
Sonawane M, Carpio Y, Geisler R, Schwarz H, Maischein HM, Nuesslein-Volhard C (2005) Zebrafish penner/lethal giant larvae 2 functions in hemidesmosome formation, maintenance of cellular morphology and growth regulation in the developing basal epidermis. Development 32:3255–3265
Sire JY, Akimendo MA (2004) Scale development in fish: a review, with description of sonic hedgehog (shh) expression in the zebrafish (Danio rerio). Int J Dev Biol 48:233–247
O’Reilly-Pol T, Johnson SL (2009) Melanocyte regeneration reveals mechanisms of adult stem cell regulation. Semin Cell Dev Biol 20:117–124
Lee Y, Nachtrab G, Klinsawat PW, Hami D, Poss KD (2010) Ras controls melanocyte expansion during zebrafish fin stripe regeneration. Dis Model Mech 3:496–503
Froehlicher M, Liedtke A, Groh KJ, Neuhauss SC, Segner H, Eggen RI (2009) Zebrafish (Danio rerio) neuromast: promising biological endpoint linking development and toxicological studies. Aquat Toxicol 95:307–319
Westerfield M (2007) The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 5th edn. University of Oregon Press, Eugene
Postlethwait JH (2007) The zebrafish genome in context: ohnologs gone missing. J Exp Zool 308B:563–577
Roch GJ, Wu S, Sherwood NM (2009) Hormones and receptors in fish: do duplicates matter? Gen Comp Endocrinol 161:3–12
Kim SH, Choi HY, So JH, Kim CH, Ho SY, Frank M, Li Q, Uitto J (2010) Zebrafish type XVII collagen: gene structures, expression profiles, and morpholino “knock-down” phenotypes. Matrix Biol 29:629–637
Seppänen A, Autio-Harmainen H, Alafuzoff I, Särkioja T, Veijola J, Hurskainen T, Bruckner-Tuderman L, Tasanen K, Majamaa K (2006) Collagen XVII is expressed in human CNS neurons. Matrix Biol 25:185–188
Has C, Kern JS (2010) Collagen XVII. Dermatol Clin 28:61–66
Sprague J, Bayraktaroglu L, Bradford Y et al (2008) The Zebrafish Information Network: the zebrafish model organism database provides expanded support for genotypes and phenotypes. Nucleic Acids Res 36:D768
Eisen JS, Smith JC (2008) Controlling morpholino experiments: don’t stop making antisense. Development 135:1735–1743
Shan G (2010) RNA interference as gene knockdown technique. Int J Biochem Cell Biol 42:1243–1251
Li Q, Frank M, Akiyama M, Shimizu H, Ho SY, Thisse C, Thisse B, Sprecher E, Uitto J (2011) Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are critical for epidermal morphogenesis in zebrafish disease model of ichthyosis. Dis Model Mech 4:777–785
Robu ME, Larson JD, Nasevicius A, Beriraghi S, Farber SA, Ekker SC (2007) p53 activation by knock down technologies. PLoS Genet 3:e78
Jiang Q, Li Q, Uitto J (2007) Aberrant mineralization of connective tissues in a mouse model of pseudoxanthoma elasticum: systemic and local regulatory factors. J Invest Dermatol 127:1392–1402
Li Q, Sadowski S, Frank M, Chai C, Väradi A, Ho SY, Lou H, Dean M, Thisse C, Thisse B, Uitto J (2010) The abcc6a gene expression is required for normal zebrafish development. J Invest Dermatol 130:2561–2568
Peterson RT, Link BA, Dowling JE, Schreiber SL (2000) Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci U S A 97:12965–12969
Burns CG, Milan DJ, Grande EJ, Rottbauer W, MacRae CA, Fishman MC (2005) High-throughput assay for small molecules that modulate zebrafish embryonic heart rate. Nat Chem Biol 1:263–264
Weinstein BM, Stemple DL, Driever W, Fishman MC (1995) Gridlock, a localized heritable vascular patterning defect in the zebrafish. Nat Med 1:1143–1147
Hong CC, Peterson QP, Hong J, Peterson RT (2006) Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Curr Biol 16:1366–1372
Peterson RT, Shaw SY, Peterson TA, Milan DJ, Zhong TP, Schreiber SL, MacRae CA, Fishman MC (2004) Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat Biotechnol 22:595–599
Stern HM, Murphey RD, Shepard JL, Amatruda JF, Straub CT, Pfaff KL, Weber G, Tallarico JA, King RW, Zon LI (2005) Small molecules that delay S phase suppress a zebrafish bmyb mutant. Nature Chem Biol 1:366–370
Acknowledgments
This work was supported by a Jefferson Intramural Pilot Research Award and Dermatology Foundation Research Career Development Award to QL. This manuscript is edited from a perspective article by the authors (7).
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Li, Q., Uitto, J. (2013). Zebrafish as a Model System to Study Heritable Skin Diseases. In: Has, C., Sitaru, C. (eds) Molecular Dermatology. Methods in Molecular Biology, vol 961. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-227-8_28
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DOI: https://doi.org/10.1007/978-1-62703-227-8_28
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