Mô hình cá zeber góp phần vào việc nghiên cứu hội chứng nhạy cảm với hormone tăng trưởng kèm theo rối loạn miễn dịch 1 (GHISID1)

Cellular and Molecular Life Sciences - Tập 80 - Trang 1-12 - 2023
Somayyeh Heidary1, Nagendra Awasthi1, Nicole Page1, Theo Allnutt1, Rowena S. Lewis2, Clifford Liongue1,3, Alister C. Ward1,3
1School of Medicine, Deakin University, Geelong, Australia
2School of Life and Environmental Sciences, Deakin University, Burwood, Australia
3IMPACT, Deakin University, Geelong, Australia

Tóm tắt

Các protein truyền tín hiệu và kích hoạt phiên mã (STAT) hoạt động ở hạ lưu của các thụ thể cytokine nhằm tạo thuận lợi cho những thay đổi về biểu hiện gen ảnh hưởng đến nhiều quá trình phát triển và duy trì cân bằng nội mô. Những bệnh nhân mang đột biến mất chức năng (LOF) trong gen STAT5B thể hiện sự chậm phát triển sau sinh do thiếu phản ứng với hormone tăng trưởng cũng như rối loạn hệ miễn dịch, một rối loạn được gọi là hội chứng nhạy cảm với hormone tăng trưởng và rối loạn miễn dịch 1 (GHISID1). Nghiên cứu này nhằm xây dựng mô hình cá zeber cho căn bệnh này bằng cách nhắm mục tiêu vào gen stat5.1 thông qua công nghệ CRISPR/Cas9 và phân tích tác động đến sự phát triển và hệ miễn dịch. Các đột biến Stat5.1 ở cá zeber có kích thước nhỏ hơn, nhưng thể hiện sự tích tụ mỡ cao hơn, đi kèm với việc điều hòa không đúng đắn các gen liên quan đến sự phát triển và chuyển hóa lipid. Những con đột biến này cũng cho thấy sự kém phát triển của quá trình tạo lympho với số lượng tế bào T giảm suốt cuộc đời, cùng với sự phá vỡ rộng rãi của khoang lympho trong giai đoạn trưởng thành, bao gồm bằng chứng về sự kích hoạt tế bào T. Tập hợp lại, những phát hiện này xác nhận rằng các đột biến Stat5.1 ở cá zeber mô phỏng các tác động lâm sàng của các đột biến LOF ở người STAT5B, thiết lập chúng thành một mô hình cho GHISID1.

Từ khóa

#STAT5B #hội chứng nhạy cảm với hormone tăng trưởng #cá zeber #đột biến LOF #hệ miễn dịch

Tài liệu tham khảo

Awasthi N, Liongue C, Ward AC (2021) STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer. J Hematol Oncol 14(1):1–17 Buitenhuis M, Coffer PJ, Koenderman L (2004) Signal transducer and activator of transcription 5 (STAT5). Int J Biochem Cell Biol 36(11):2120–2124 Baik M, Yu JH, Hennighausen L (2011) Growth hormone-STAT5 regulation of growth, hepatocellular carcinoma, and liver metabolism. Annals NY Acad Sci 1229:29–37 Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA et al (1997) Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 94(14):7239–7244 Liu X, Robinson GW, Wagner K-U, Garrett L, Wynshaw-Boris A, Hennighausen L (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev 11:179–186 Maurer B, Kollmann S, Pickem J, Hoelbl-Kovacic A, Sexl V (2019) STAT5A and STAT5B-twins with different personalities in hematopoiesis and leukemia. Cancers 11(11):1726 Hwa V (2021) Human growth disorders associated with impaired GH action: defects in STAT5B and JAK2. Mol Cell Endocrinol 519:111063 David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJ et al (2011) Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocrine Rev 32(4):472–497 Lin S, Li C, Li C, Zhang X (2018) Growth hormone receptor mutations related to individual dwarfism. Int J Mol Sci 19(5):1433 Woods KA, Camacho-Hübner C, Savage MO, Clark AJ (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. New Engl J Med 335(18):1363–1367 Domené HM, Bengolea SV, Martínez AS, Ropelato MG, Pennisi P, Scaglia P et al (2004) Deficiency of the circulating insulin-like growth factor system associated with inactivation of the acid-labile subunit gene. New Engl J Med 350(6):570–577 Dauber A, Muñoz-Calvo MT, Barrios V, Domené HM, Kloverpris S, Serra-Juhé C et al (2016) Mutations in pregnancy-associated plasma protein A2 cause short stature due to low IGF-I availability. EMBO Mol Med 8(4):363–374 Hwa V (2016) STAT5B deficiency: impacts on human growth and immunity. Growth Hormone IGF Res 28:16–20 Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J et al (2003) Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 349:1139–1147 Vidarsdottir S, Walenkamp MJ, Pereira AM, Karperien M, van Doorn J, van Duyvenvoorde HA et al (2006) Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation. J Clin Endocrinol Metab 91:3482–3485 Bernasconi A, Marino R, Ribas A, Rossi J, Ciaccio M, Oleastro M et al (2006) Characterization of immunodeficiency in a patient with growth hormone insensitivity secondary to a novel STAT5b gene mutation. Pediatrics 118(5):1584–1592 Klammt J, Neumann D, Gevers EF, Andrew SF, Schwartz ID, Rockstroh D et al (2018) Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nat Commun 9(1):1–10 Rasighaemi P, Basheer F, Liongue C, Ward AC (2015) Zebrafish as a model for leukemia and other hematopoietic disorders. J Hematol Oncol 8:29 Zang L, Maddison LA, Chen W (2018) Zebrafish as a model for obesity and diabetes. Front Cell Dev Biol 6:91 Liongue C, Ward AC (2007) Evolution of class I cytokine receptors. BMC Evol Biol 7:120 Liongue C, Ward AC (2013) Evolution of the Jak-Stat pathway. JAK-STAT 2:e22756 Lewis RS, Ward AC (2004) Conservation, duplication and divergence of the zebrafish stat5 genes. Gene 338(1):65–74 Lawrence C (2011) Advances in zebrafish husbandry and management. Meth Cell Biol 104:429–451 Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD et al (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotech 31(3):227–229 Krypuy M, Ahmed AA, Etemadmoghadam D, Hyland SJ, DeFazio A, Australian Ovarian Cancer Study G et al (2007) High resolution melting for mutation scanning of TP53 exons 5–8. BMC Cancer 7:168 Parichy DM, Elizondo MR, Mills MG, Gordon TN, Engeszer RE (2009) Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev Dyn 238(12):2975–3015 Tingaud-Sequeira A, Ouadah N, Babin PJ (2011) Zebrafish obesogenic test: a tool for screening molecules that target adiposity. J Lipid Res 52(9):1765–1772 Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509 Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C (2001) An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods 25(4):386–401 Thisse C, Thisse B (2008) High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc 3(1):59–69 Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30(15):2114–2120 Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140 Fernandes AD, Macklaim JM, Linn TG, Reid G, Gloor GB (2013) ANOVA-like differential expression (ALDEx) analysis for mixed population RNA-Seq. PLoS ONE 8(7):e67019 Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD (2019) PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res 47(D1):D419–D426 Sertori R, Trengove M, Basheer F, Ward AC, Liongue C (2016) Genome editing in zebrafish: a practical overview. Brief Funct Genomics 15(4):322–330 Chen AT, Zon LI (2009) Zebrafish blood stem cells. J Cell Biochem 108(1):35–42 Herzog W, Zeng X, Lele Z, Sonntag C, Ting J-W, Chang C-Y et al (2003) Adenohypophysis formation in the zebrafish and its dependence on sonic hedgehog. Dev Biol 254(1):36–49 Liu NA, Liu Q, Wawrowsky K, Yang Z, Lin S, Melmed S (2006) Prolactin receptor signaling mediates the osmotic response of embryonic zebrafish lactotrophs. Mol Endocrinol 20(4):871–880 Li J, Wu P, Liu Y, Wang D, Cheng CH (2014) Temporal and spatial expression of the four Igf ligands and two Igf type 1 receptors in zebrafish during early embryonic development. Gene Expr Patterns 15(2):104–111 Yu Q, Huo J, Zhang Y, Liu K, Cai Y, Xiang T et al (2020) Tamoxifen-induced hepatotoxicity via lipid accumulation and inflammation in zebrafish. Chemosphere 239:124705 Shochat C, Wang Z, Mo C, Nelson S, Donaka R, Huang J et al (2021) Deletion of SREBF1, a functional bone-muscle pleiotropic gene, alters bone density and lipid signaling in zebrafish. Endocrinology 162(1):bqaa189 Willett CE, Kawasaki H, Amemiya CT, Lin S, Steiner LA (2001) Ikaros expression as a marker for lymphoid progenitors during zebrafish development. Dev Dyn 222(4):694–698 Willett CE, Cherry JJ, Steiner L (1997) Characterization and expression of the recombination activating genes (rag1 and rag2) of zebrafish. Immunogenetics 45(6):394–404 Danilova N, Hohman VS, Sacher F, Ota T, Willett CE, Steiner LA (2004) T cells and the thymus in developing zebrafish. Dev Comp Immunol 28(7–8):755–767 Moore FE, Garcia EG, Lobbardi R, Jain E, Tang Q, Moore JC et al (2016) Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish. J Exp Med 213(6):979–992 Rieder SA, Metidji A, Glass DD, Thornton AM, Ikeda T, Morgan BA et al (2015) Eos is redundant for regulatory T cell function but plays an important role in IL-2 and Th17 production by CD4+ conventional T cells. J Immunol 195(2):553–563 Kasheta M, Painter CA, Moore FE, Lobbardi R, Bryll A, Freiman E et al (2017) Identification and characterization of T reg–like cells in zebrafish. J Exp Med 214(12):3519–3530 Pugliese-Pires PN, Tonelli CA, Dora JM, Silva PC, Czepielewski M, Simoni G et al (2010) A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings. Eur J Endocrinol 163(2):349 Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D et al (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93:841–850 McMenamin SK, Minchin JE, Gordon TN, Rawls JF, Parichy DM (2013) Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini. Endocrinology 154(4):1476–1487 List EO, Basu R, Duran-Ortiz S, Krejsa J, Jensen EA (2021) Mouse models of growth hormone deficiency. Rev Endocrine Metab Disord 22(1):3–16 List EO, Sackmann-Sala L, Berryman DE, Funk K, Kelder B, Gosney ES et al (2011) Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse. Endocrinol Rev 32(3):356–386 Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T et al (2002) Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA 99(7):4465–4470 Livingstone C, Borai A (2014) Insulin-like growth factor-II: its role in metabolic and endocrine disease. Clin Endocrinol 80(6):773–781 Nornberg BF, Figueiredo MA, Marins LF (2016) Expression profile of IGF paralog genes in liver and muscle of a GH-transgenic zebrafish. Gen Compar Endocrinol 226:36–41 Zeng N, Bao J, Shu T, Shi C, Zhai G, Xia J et al (2022) Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish. Front Endocrinol 13:1645 Hagmayer A, Furness AI, Reznick DN, Pollux BJ (2018) Maternal size and body condition predict the amount of post-fertilization maternal provisioning in matrotrophic fish. Ecol Evol 8(24):12386–12396 Hinrichs A, Kessler B, Kurome M, Blutke A, Kemter E, Bernau M et al (2018) Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver. Mol Metab 11:113–128 Lanes R, Soros A, Gunczler P, Paoli M, Carrillo E, Villaroel O et al (2006) Growth hormone deficiency, low levels of adiponectin, and unfavorable plasma lipid and lipoproteins. J Pediatrics 149(3):324–329 Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A (2008) Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol - Endocrinol Metab 295(2):E385–E392 Rowland JE, Lichanska AM, Kerr LM, White M, d’Aniello EM, Maher SL et al (2005) In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol 25(1):66–77 Mueller KM, Kornfeld JW, Friedbichler K, Blaas L, Egger G, Esterbauer H et al (2011) Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice. Hepatology 54(4):1398–1409 Nadeau K, Hwa V, Rosenfeld RG (2011) STAT5b deficiency: an unsuspected cause of growth failure, immunodeficiency, and severe pulmonary disease. J Pediatrics 158(5):701–708 Cohen AC, Nadeau KC, Tu W, Hwa V, Dionis K, Bezrodnik L et al (2006) Decreased accumulation and regulatory function of CD4+ CD25high T cells in human STAT5b deficiency. J Immunol 177(5):2770–2774 Scaglia PA, Martínez AS, Feigerlová E, Bezrodnik L, Gaillard MI, Di Giovanni D et al (2012) A novel missense mutation in the SH2 domain of the STAT5B gene results in a transcriptionally inactive STAT5b associated with severe IGF-I deficiency, immune dysfunction, and lack of pulmonary disease. J Clin Endocrinol 97(5):E830–E839 Jenks JA, Seki S, Kanai T, Huang J, Morgan AA, Scalco RC et al (2013) Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells. Clin Immunol 148(2):227–236 Snow JW, Abraham N, Ma MC, Herndier BG, Pastuszak AW, Goldsmith MA (2003) Loss of tolerance and autoimmunity affecting multiple organs in STAT5A/5B-deficient mice. J Immunol 171(10):5042–5050 Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D et al (1999) Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10(2):249–259 Wiedemann GM, Grassmann S, Lau CM, Rapp M, Villarino AV, Friedrich C et al (2020) Divergent role for STAT5 in the adaptive responses of natural killer cells. Cell Rep 33(11):108498 Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS et al (1993) Interleukin-2 receptor g chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73:147–157 Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301(5900):527–530 Sertori R, Jones R, Basheer F, Rivera L, Dawson S, Loke S et al (2022) Generation and characterization of a zebrafish IL-2Rgc SCID model. Int J Mol Sci 23(4):2385 Yao Z, Cui Y, Watford WT, Bream JH, Yamaoka K, Hissong BD et al (2006) Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci USA 104:1000–1004 Sertori R, Liongue C, Basheer F, Lewis KL, Rasighaemi P, de Coninck D et al (2016) Conserved IL-2Rgc signaling mediates lymphopoiesis in zebrafish. J Immunol 196(1):135–143 Basheer F, Bulleeraz V, Ngo VQT, Liongue C, Ward AC (2022) In vivo impact of JAK3 A573V mutation revealed using zebrafish. Cell Mol Life Sci 79(6):322 Xiong S, Mei J, Huang P, Jing J, Li Z, Kang J et al (2017) Essential roles of stat5.1/stat5b in controlling fish somatic growth. J Genet Genom 44(12):577–585 Huang P, Xiong S, Kang J, Mei J, Gui JF (2018) Stat5b regulates sexually dimorphic gene expression in zebrafish liver. Front Physiol 9:676 Braun TP, Okhovat M, Coblentz C, Carratt SA, Foley A, Schonrock Z et al (2022) Author correction: myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia. Nat Commun 13(1):3471 Luo Y, Alexander M, Gadina M, O’Shea JJ, Meylan F, Schwartz DM (2021) JAK-STAT signaling in human disease: from genetic syndromes to clinical inhibition. J Allergy Clin Immunol 148(4):911–925 Ma AC, Fan A, Ward AC, Liongue C, Lewis RS, Cheng SH et al (2009) A novel zebrafish jak2a(V581F) model shared features of human JAK2(V617F) polycythemia vera. Exp Hematol 37(12):1379–1386 Lewis RS, Stephenson SEM, Ward AC (2006) Constitutive activation of zebrafish stat5 expands hematopoietic cell populations in vivo. Exp Hematol 34(2):179–187 Xiong ST, Wu JJ, Jing J, Huang PP, Li Z, Mei J et al (2017) Loss of stat3 function leads to spine malformation and immune disorder in zebrafish. Sci Bull 62(3):185–196 Vogel TP, Milner JD, Cooper MA (2015) The ying and yang of STAT3 in human disease. J Clin Immunol 35(7):615–623