Advantages of Ciona intestinalis as a Model Organism and Its Applications

doi:10.12300/j.issn.1674-5817.2023.159

Abstract

Abstract:

With the continuous development of experimental biology, the limitations of commonly utilized model organisms are becoming increasingly apparent. Discrepancies between research conducted on laboratory animals and humans significantly impede the translational application of findings derived from animal experiments. This review introduces ascidian Ciona intestinalis as a novel model organism, an invertebrate that is evolutionarily closest to vertebrates and is a sister group to vertebrates. The review summarizes recent research progress on Ciona intestinalis in various fields to illustrate the significant advantages and promising application prospects of it as a model organism. The research progress outlined in the review mainly encompasses: (1) The whole-genome sequencing of Ciona intestinalis has been determined and numerous related databases have been established. Various embryonic gene editing technologies have been successfully applied, making it an animal model easy to manipulate genetically and study the functions and interactions of target genes visually. (2) In the field of neurobiology, Ciona intestinalis boasts a central nervous system structure similar to that of vertebrates and possesses numerous homologous neuropeptides and hormone molecules. These features grant it an edge in exploring the mechanisms and functional evolution of endocrine and neuroendocrine-related molecules. Additionally, the sensitivity and habituation of its larvae to light stimulation provide an avenue for exploring mechanisms related to behavioral plasticity. (3) In the field of immunology, Ciona intestinalis possesses a mature innate immune system and has evolved precursor genes to the adaptive immune system, with a relatively simple coding of immune-related genes. These features make it an exemplary model organism for immunological studies. (4) In the field of developmental biology, many studies have focused on the notochord development process in Ciona intestinalis and the regulatory mechanisms of gene expression within it, indicating common evolutionary developmental strategies among chordates. Additionally, insights into its heart development also significantly enhance our comprehension on the genetic network of human heart development. (5) In medical research, the ability of Ciona intestinalis to regenerate its neural complex and siphon, as well as the resilience of its heart to recover contractile function from substantial damage, renders it a valuable animal model for the study of regeneration and heart injury. It also has unique advantages as a research model for Alzheimer's disease and new drug development. Furthermore, its brief five-month lifespan facilitates the observation and recording of the entire aging process and the exploration of the effects of various factors on aging. In summary, this review aims to demonstrate that Ciona intestinalis stands out as a model organism with unique attributes and is expected to play a significant role in a wider range of scientific research areas.

Key words: Ciona intestinalis, Model organism, Neurobiology, Immunology, Developmental biology

CLC Number:

Q95-33

Ruiqi LI,Han DUAN,Luo GAN,et al. Advantages of Ciona intestinalis as a Model Organism and Its Applications[J]. Laboratory Animal and Comparative Medicine, 2024, 44(2): 162-179. DOI: 10.12300/j.issn.1674-5817.2023.159.

Figures/Tables 6

References 77

1	DENOEUD F, HENRIET S, MUNGPAKDEE S, et al. Plasticity of animal genome architecture unmasked by rapid evolution of a pelagic tunicate[J]. Science, 2010, 330( 6009): 1381- 1385. DOI: 10.1126/science.1194167 .
2	DELSUC F, BRINKMANN H, CHOURROUT D, et al. Tunicates and not cephalochordates are the closest living relatives of vertebrates[J]. Nature, 2006, 439( 7079): 965- 968. DOI: 10.1038/nature04336 .
3	TREEN N, SHIMOBAYASHI S F, EEFTENS J, et al. Properties of repression condensates in living Ciona embryos[J]. Nat Commun, 2021, 12( 1): 1561. DOI: 10.1038/s41467-021-21606-5 .
4	SATOU Y, NAKAMURA R, YU D L, et al. A nearly complete genome of Ciona intestinalis type A (C. robusta) reveals the contribution of inversion to chromosomal evolution in the genus Ciona [J]. Genome Biol Evol, 2019, 11( 11): 3144- 3157. DOI: 10.1093/gbe/evz228 .
5	DEHAL P, SATOU Y, CAMPBELL R K, et al. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins[J]. Science, 2002, 298( 5601): 2157- 2167. DOI: 10.1126/science.1080049 .
6	SATOU Y, TOKUOKA M, ODA-ISHII I, et al. A manually curated gene model set for an ascidian, Ciona robusta ( Ciona intestinalis type a)[J]. Zoolog Sci, 2022, 39( 3): 253- 260. DOI: 10.2108/zs210102 .
7	SATOH N, SATOU Y, DAVIDSON B, et al. Ciona intestinalis: an emerging model for whole-genome analyses[J]. Trends Genet, 2003, 19( 7): 376- 381. DOI: 10.1016/S0168-9525(03)00144-6 .
8	LIBERTI A, NATARAJAN O, ATKINSON C G F, et al. Reflections on the use of an invertebrate chordate model system for studies of gut microbial immune interactions[J]. Front Immunol, 2021, 12: 642687. DOI: 10.3389/fimmu. 2021. 642687 .
9	MATSUBARA S, KAWADA T, SAKAI T, et al. The significance of Ciona intestinalis as a stem organism in integrative studies of functional evolution of the chordate endocrine, neuroendocrine, and nervous systems[J]. Gen Comp Endocrinol, 2016, 227: 101- 108. DOI: 10.1016/j.ygcen.2015.05.010 .
10	HAYWOOD C A, MOON H P, MILLAR R H. Reversal of the heart-beat in Tunicates[J]. Nature, 1953, 172( 4366): 40- 41. DOI: 10.1038/172040b0 .
11	KALK M. The organization of a tunicate heart[J]. Tissue Cell, 1970, 2( 1): 99- 118. DOI: 10.1016/s0040-8166(70)80010-6 .
12	EALES J G. Iodine metabolism and thyroid-related functions in organisms lacking thyroid follicles: are thyroid hormones also vitamins?[J]. Proc Soc Exp Biol Med, 1997, 214( 4): 302- 317. DOI: 10.3181/00379727-214-44098 .
13	PASSAMANECK Y J, DI GREGORIO A. Ciona intestinalis: chordate development made simple[J]. Dev Dyn, 2005, 233( 1): 1- 19. DOI: 10.1002/dvdy.20300 .
14	YOSHIDA K, TREEN N. TALEN-based knockout system[M]//SASAKURA Y, ed. Transgenic Ascidians. Singapore: Springer, 2018: 131- 139. DOI: 10.1007/978-981-10-7545-2_12 .
15	NAKASHIMA K, YAMADA L, SATOU Y, et al. The evolutionary origin of animal cellulose synthase[J]. Dev Genes Evol, 2004, 214( 2): 81- 88. DOI: 10.1007/s00427-003-0379-8 .
16	GANDHI S, RAZY-KRAJKA F, CHRISTIAEN L, et al. CRISPR knockouts in Ciona embryos[J]. Adv Exp Med Biol, 2018, 1029: 141- 152. DOI: 10.1007/978-981-10-7545-2_13 .
17	SASAKURA Y, HORIE T. Improved genome editing in the ascidian Ciona with CRISPR/Cas9 and TALEN[J]. Methods Mol Biol, 2023, 2637: 375- 388. DOI: 10.1007/978-1-0716-3016-7_28 .
18	SATOU Y, IMAI K S, SATOH N. Action of morpholinos in Ciona embryos[J]. Genesis, 2001, 30( 3): 103- 106. DOI: 10.1002/gene.1040 .
19	HOZUMI A, KAWAI N, YOSHIDA R, et al. Efficient transposition of a single Minos transposon copy in the genome of the ascidian Ciona intestinalis with a transgenic line expressing transposase in eggs[J]. Dev Dyn, 2010, 239( 4): 1076- 1088. DOI: 10.1002/dvdy.22254 .
20	KOBAYASHI K, SATOU Y. Microinjection of exogenous nucleic acids into eggs: Ciona species[M]//SASAKURA Y. Transgenic Ascidians. Singapore: Springer, 2018: 5- 13.10. 1007/978-981-10-7545-2_ 2.
21	ZELLER R W. Electroporation in ascidians: history, theory and protocols[M]//SASAKURA Y. Transgenic Ascidians. Singapore: Springer, 2018: 37- 48.10. 1007/978-981-10-7545-2_ 5.
22	HORIE T, NAKAGAWA M, SASAKURA Y, et al. Cell type and function of neurons in the ascidian nervous system[J]. Dev Growth Differ, 2009, 51( 3): 207- 220. DOI: 10.1111/j.1440-169X.2009.01105.x .
23	HORIE T, NAKAGAWA M, SASAKURA Y, et al. Simple motor system of the ascidian larva: neuronal complex comprising putative cholinergic and GABAergic/glycinergic neurons[J]. Zoolog Sci, 2010, 27( 2): 181- 190. DOI: 10.2108/zsj.27.181 .
24	STOLFI A, LEVINE M. Neuronal subtype specification in the spinal cord of a protovertebrate[J]. Development, 2011, 138( 5): 995- 1004. DOI: 10.1242/dev.061507 .
25	IKUTA T, SAIGA H. Dynamic change in the expression of developmental genes in the ascidian central nervous system: revisit to the tripartite model and the origin of the midbrain-hindbrain boundary region[J]. Dev Biol, 2007, 312( 2): 631- 643. DOI: 10.1016/j.ydbio.2007.10.005 .
26	IMAI K S, STOLFI A, LEVINE M, et al. Gene regulatory networks underlying the compartmentalization of the Ciona central nervous system[J]. Development, 2009, 136( 2): 285- 293. DOI: 10.1242/dev.026419 .
27	LEMAIRE L A, CAO C, YOON P H, et al. The hypothalamus predates the origin of vertebrates[J]. Sci Adv, 2021, 7( 18): eabf7452. DOI: 10.1126/sciadv.abf7452 .
28	OSUGI T, SASAKURA Y, SATAKE H. The nervous system of the adult ascidian Ciona intestinalis Type A ( Ciona robusta): insights from transgenic animal models[J]. PLoS One, 2017, 12( 6): e0180227. DOI: 10.1371/journal.pone.0180227 .
29	TSUDA M, KAWAKAMI I, SHIRAISHI S. Sensitization and habituation of the swimming behavior in ascidian larvae to light[J]. Zoolog Sci, 2003, 20( 1): 13- 22. DOI: 10.2108/zsj.20.13 .
30	BORBA C, KOURAKIS M J, SCHWENNICKE S, et al. Fold change detection in visual processing[J]. Front Neural Circuits, 2021, 15: 705161. DOI: 10.3389/fncir.2021.705161 .
31	SATAKE H, MATSUBARA S, SHIRAISHI A, et al. Neuropeptides, peptide hormones, and their receptors of a tunicate, Ciona intestinalis [J]. Results Probl Cell Differ, 2019, 68: 107- 125. DOI: 10.1007/978-3-030-23459-1_5 .
32	AOYAMA M, KAWADA T, FUJIE M, et al. A novel biological role of tachykinins as an up-regulator of oocyte growth: identification of an evolutionary origin of tachykininergic functions in the ovary of the ascidian, Ciona intestinalis [J]. Endocrinology, 2008, 149( 9): 4346- 4356. DOI: 10.1210/en.2008-0323 .
33	KAWADA T, OGASAWARA M, SEKIGUCHI T, et al. Peptidomic analysis of the central nervous system of the protochordate, Ciona intestinalis: homologs and prototypes of vertebrate peptides and novel peptides[J]. Endocrinology, 2011, 152( 6): 2416- 2427. DOI: 10.1210/en.2010-1348 .
34	HOZUMI A, MATSUNOBU S, MITA K R, et al. GABA-induced GnRH release triggers chordate metamorphosis[J]. Curr Biol, 2020, 30( 8): 1555- 1561.e4. DOI: 10.1016/j.cub.2020.02.003 .
35	AZUMI K, DE SANTIS R, DE TOMASO A, et al. Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: "waiting for Godot"[J]. Immunogenetics, 2003, 55( 8): 570- 581. DOI: 10.1007/s00251-003-0606-5 .
36	SATAKE H, MATSUBARA S, SHIRAISHI A, et al. Peptide receptors and immune-related proteins expressed in the digestive system of a urochordate, Ciona intestinalis [J]. Cell Tissue Res, 2019, 377( 3): 293- 308. DOI: 10.1007/s00441-019-03024-8 .
37	LONGO V, PARRINELLO D, LONGO A, et al. The conservation and diversity of ascidian cells and molecules involved in the inflammatory reaction: the Ciona robusta model[J]. Fish Shellfish Immunol, 2021, 119: 384- 396. DOI: 10.1016/j.fsi.2021.10.022 .
38	SATOH N. Innate immune system and blood cells[M/OL]//SATOH N.Developmental genomics of ascidians.Hoboken:John Wiley & Sons,Inc., 2013:159-165.(2013-12-05)[2023-11-01].https://onlinelibrary.wiley.com/doi/abs/10.1002/9781118656129.ch15.
39	DI BELLA M A, FEDDERS H, DE LEO G, et al. Localization of antimicrobial peptides in the tunic of Ciona intestinalis (Ascidiacea, Tunicata) and their involvement in local inflammatory-like reactions[J]. Results Immunol, 2011, 1( 1): 70- 75. DOI: 10.1016/j.rinim.2011.09.001 .
40	KASAHARA M, SUZUKI T, PASQUIER L D. On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates[J]. Trends Immunol, 2004, 25( 2): 105- 111. DOI: 10.1016/j.it.2003.11.005 .
41	DISHAW L J, CANNON J P, LITMAN G W, et al. Immune-directed support of rich microbial communities in the gut has ancient roots[J]. Dev Comp Immunol, 2014, 47( 1): 36- 51. DOI: 10.1016/j.dci.2014.06.011 .
42	VIZZINI A, PARRINELLO D, SANFRATELLO M A, et al. Ciona intestinalis peroxinectin is a novel component of the peroxidase-cyclooxygenase gene superfamily upregulated by LPS[J]. Dev Comp Immunol, 2013, 41( 1): 59- 67. DOI: 10.1016/j.dci.2013.03.015 .
43	VIZZINI A, BONURA A, LONGO V, et al. Isolation of a novel LPS-induced component of the ML superfamily in Ciona intestinalis [J]. Dev Comp Immunol, 2015, 53( 1): 70- 78. DOI: 10.1016/j.dci.2015.06.018 .
44	VIZZINI A, BONURA A, LA PAGLIA L, et al. Transcriptomic analyses reveal 2 and 4 family members of cytochromes P450 (CYP) involved in LPS inflammatory response in pharynx of Ciona robusta [J]. Int J Mol Sci, 2021, 22( 20): 11141. DOI: 10.3390/ijms222011141 .
45	BONURA A, VIZZINI A, VLAH S, et al. Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis, modulates responses of the human immune system[J]. Immunobiology, 2018, 223( 2): 210- 219. DOI: 10.1016/j.imbio. 2017.10.024 .
46	ARIZZA V, BONURA A, LA PAGLIA L, et al. Transcriptional and in silico analyses of MIF cytokine and TLR signalling interplay in the LPS inflammatory response of Ciona robusta [J]. Sci Rep, 2020, 10( 1): 11339. DOI: 10.1038/s41598-020-68339-x .
47	VIZZINI A, DUMAS F, DI FALCO F, et al. Evolutionary and transcriptional analyses of a pentraxin-like component family involved in the LPS inflammatory response of Ciona robusta [J]. Fish Shellfish Immunol, 2021, 111: 94- 101. DOI: 10.1016/j.fsi.2021.01.014 .
48	STEMPLE D L. Structure and function of the notochord: an essential organ for chordate development[J]. Development, 2005, 132( 11): 2503- 2512. DOI: 10.1242/dev.01812 .
49	LU Q X, BHATTACHAN P, DONG B. Ascidian notochord elongation[J]. Dev Biol, 2019, 448( 2): 147- 153. DOI: 10.1016/j.ydbio.2018.11.009 .
50	DONG B, HORIE T, DENKER E, et al. Tube formation by complex cellular processes in Ciona intestinalis notochord[J]. Dev Biol, 2009, 330( 2): 237- 249. DOI: 10.1016/j.ydbio.2009.03.015 .
51	MUNRO E M, ODELL G M. Polarized basolateral cell motility underlies invagination and convergent extension of the ascidian notochord[J]. Development, 2002, 129( 1): 13- 24. DOI: 10.1242/dev.129.1.13 .
52	BAGNAT M, CHEUNG I D, MOSTOV K E, et al. Genetic control of single lumen formation in the zebrafish gut[J]. Nat Cell Biol, 2007, 9: 954- 960. DOI: 10.1038/ncb1621 .
53	WANG Z Q, OUYANG X K, TAN Z C, et al. Quantitative phosphoproteomics reveals the requirement of DYRK1-mediated phosphorylation of ion transport- and cell junction-related proteins for notochord lumenogenesis in ascidian[J]. Cells, 2023, 12( 6): 921. DOI: 10.3390/cells12060921 .
54	DI G A. The notochord gene regulatory network in chordate evolution: conservation and divergence from Ciona to vertebrates[J]. Curr Top Dev Biol, 2020, 139: 325- 374. DOI: 10.1016/bs.ctdb.2020.01.002 .
55	OLIVO P, PALLADINO A, RISTORATORE F, et al. Brain sensory organs of the ascidian Ciona robusta: structure, function and developmental mechanisms[J]. Front Cell Dev Biol, 2021, 9: 701779. DOI: 10.3389/fcell.2021.701779 .
56	ISLAS J F, LIU Y, WENG K C, et al. Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors[J]. Proc Natl Acad Sci USA, 2012, 109( 32): 13016- 13021. DOI: 10.1073/pnas.1120299109 .
57	WANG W, NIU X, STUART T, et al. A single-cell transcriptional roadmap for cardiopharyngeal fate diversification[J]. Nat Cell Biol, 2019, 21( 6): 674- 686. DOI: 10.1038/s41556-019-0336-z .
58	AUGER H, SASAKURA Y, JOLY J S, et al. Regeneration of oral siphon pigment organs in the ascidian Ciona intestinalis [J]. Dev Biol, 2010, 339( 2): 374- 389. DOI: 10.1016/j.ydbio.2009. 12.040 .
59	JEFFERY W R. Closing the wounds: one hundred and twenty five years of regenerative biology in the ascidian Ciona intestinalis [J]. Genesis, 2015, 53( 1): 48- 65. DOI: 10.1002/dvg. 22799 .
60	JEFFERY W R. Distal regeneration involves the age dependent activity of branchial sac stem cells in the ascidian Ciona intestinalis [J]. Regeneration, 2015, 2( 1): 1- 18. DOI: 10.1002/reg2.26 .
61	JEFFERY W R. Regeneration, stem cells, and aging in the tunicate Ciona: insights from the oral siphon[J]. Int Rev Cell Mol Biol, 2015, 319: 255- 282. DOI: 10.1016/bs.ircmb.2015.06.005 .
62	JEFFERY W R, GORIČKI Š. Apoptosis is a generator of Wnt-dependent regeneration and homeostatic cell renewal in the ascidian Ciona [J]. Biol Open, 2021, 10( 4): bio058526. DOI: 10.1242/bio.058526 .
63	JEFFERY W R, LI B, NG M, et al. Differentially expressed chaperone genes reveal a stress response required for unidirectional regeneration in the basal chordate Ciona [J]. BMC Biol, 2023, 21( 1): 148. DOI: 10.1186/s12915-023-01633-y .
64	BOLLNER T, BEESLEY P W, THORNDYKE M C. Pattern of substance P- and cholecystokinin-like immunoreactivity during regeneration of the neural complex in the ascidian Ciona intestinalis [J]. J Comp Neurol, 1992, 325( 4): 572- 580. DOI: 10.1002/cne.903250409 .
65	DAHLBERG C, AUGER H, DUPONT S, et al. Refining the Ciona intestinalis model of central nervous system regeneration[J]. PLoS One, 2009, 4( 2): e4458. DOI: 10.1371/journal.pone.0004458 .
66	JOLY J S. Aquatic model organisms in neurosciences: the genome-editing revolution[M]// Genome Editing in Neurosciences. Cham: Springer, 2017: 21- 29.10. 1007/978-3-319-60192-2_ 2.
67	HARDY J A, HIGGINS G A. Alzheimer's disease: the amyloid cascade hypothesis[J]. Science, 1992, 256( 5054): 184- 185. DOI: 10.1126/science.1566067 .
68	SCHNABEL J. Amyloid: little proteins, big clues[J]. Nature, 2011, 475( 7355): S12- S14. DOI: 10.1038/475S12a .
69	VIRATA M J, ZELLER R W. Ascidians: an invertebrate chordate model to study Alzheimer's disease pathogenesis[J]. Dis Model Mech, 2010, 3( 5-6): 377- 385. DOI: 10.1242/dmm.003434 .
70	GÖTZ J, STREFFER J R, DAVID D, et al. Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy[J]. Mol Psychiatry, 2004, 9( 7): 664- 683. DOI: 10.1038/sj.mp.4001508 .
71	SCHUSTER K J, CHRISTIAEN L. The chordate origins of heart regeneration[J]. bioRxiv, 2023: 2023.09. 19. 558507. DOI: 10.1101/2023.09.19.558507 .
72	GARCIA J, CALLEWAERT N, BORSIG L. P-selectin mediates metastatic progression through binding to sulfatides on tumor cells[J]. Glycobiology, 2007, 17( 2): 185- 196. DOI: 10.1093/glycob/cwl059 .
73	OZAWA H, SONODA Y, KATO S, et al. Sulfatides inhibit adhesion, migration, and invasion of murine melanoma B16F10 cell line in vitro [J]. Biol Pharm Bull, 2012, 35( 11): 2054- 2058. DOI: 10.1248/bpb.b12-00492 .
74	CHENG L Y, LIU M, WANG C C, et al. CI₄31, an aqueous compound from Ciona intestinalis L., induces apoptosis through a mitochondria-mediated pathway in human hepatocellular carcinoma cells[J]. Evid Based Complement Alternat Med, 2011, 2011: 292873. DOI: 10.1155/2011/292873 .
75	FEDDERS H, MICHALEK M, GRÖTZINGER J, et al. An exceptional salt-tolerant antimicrobial peptide derived from a novel gene family of haemocytes of the marine invertebrate Ciona intestinalis [J]. Biochem J, 2008, 416( 1): 65- 75. DOI: 10.1042/BJ20080398 .
76	JENA P, MISHRA B, LEIPPE M, et al. Membrane-active antimicrobial peptides and human placental lysosomal extracts are highly active against mycobacteria[J]. Peptides, 2011, 32( 5): 881- 887. DOI: 10.1016/j.peptides.2011.03.002 .
77	CONSORTIUM T M. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse[J]. Nature, 2020, 583( 7817): 590- 595. DOI: 10.1038/s41586-020-2496-1 .

资源名称 Resource names	网址 Website	类型 Type	主要内容 Main content
Joint genome institute	https://genome.jgi.doe.gov/portal/	数据库	基因组
Ghost Database	http://ghost.zool.kyoto-u.ac.jp/cgi-bin/gb2/gbrowse/kh	数据库（日语）	基因组和cDNA
Aniseed genome browser	http://www.aniseed.cnrs.fr/	数据库	基因组
Smith research lab	http://labs.mcdb.ucsb.edu/smith/william	公众号	神经系统发育和功能
UniProt	https://www.uniprot.org/	数据库	蛋白质组
Ensemble	http://asia.ensemble.org	数据库	基因组
NCBI	http://www.ncbi.nlm.nih.gov/dbEST/dbEST_summary.html	数据库	基因的时空表达信息
NBRP	http://nbrp.jp/	数据库（日语）	cDNA
Database of Tunicate Gene Regulation	http://dbtgr.hgc.jp/	数据库	组织特异性基因5'侧翼的顺式调控元件数据库
NCBI	http://www.ncbi.nlm.nih.gov/geo/	数据库	基因表达谱
Tefor	http://crispor.tefor.vet	数据库	CRISPOR引物在线设计
PrimerX	http://www.bioinformatics.org/primerx/cgi-bin/DNA_1.cgi	数据库	基因突变引物在线设计
EDomics	http://edomics.qnlm.ac/#/home	数据库	基因组和转录组等

资源名称 Resource names	网址 Website	类型 Type	主要内容 Main content
Joint genome institute	https://genome.jgi.doe.gov/portal/	数据库	基因组
Ghost Database	http://ghost.zool.kyoto-u.ac.jp/cgi-bin/gb2/gbrowse/kh	数据库（日语）	基因组和cDNA
Aniseed genome browser	http://www.aniseed.cnrs.fr/	数据库	基因组
Smith research lab	http://labs.mcdb.ucsb.edu/smith/william	公众号	神经系统发育和功能
UniProt	https://www.uniprot.org/	数据库	蛋白质组
Ensemble	http://asia.ensemble.org	数据库	基因组
NCBI	http://www.ncbi.nlm.nih.gov/dbEST/dbEST_summary.html	数据库	基因的时空表达信息
NBRP	http://nbrp.jp/	数据库（日语）	cDNA
Database of Tunicate Gene Regulation	http://dbtgr.hgc.jp/	数据库	组织特异性基因5'侧翼的顺式调控元件数据库
NCBI	http://www.ncbi.nlm.nih.gov/geo/	数据库	基因表达谱
Tefor	http://crispor.tefor.vet	数据库	CRISPOR引物在线设计
PrimerX	http://www.bioinformatics.org/primerx/cgi-bin/DNA_1.cgi	数据库	基因突变引物在线设计
EDomics	http://edomics.qnlm.ac/#/home	数据库	基因组和转录组等

免疫系统组成 Immune system composition	玻璃海鞘 Ciona intestinalis		人 Homo sapiens		进化差别 Evolutionary difference
免疫系统组成 Immune system composition	分子 Molecules	作用 Function	分子 Molecules	作用 Function	进化差别 Evolutionary difference
免疫识别分子 Immune recognition molecules	TLR	介导免疫应答	TLR	介导免疫应答	人类TLR具有更多亚型
	凝集素	特异性结合糖蛋白	-	-	不存在同源分子
	酚氧化酶	杀死细菌，合成黑色素	-	-	不存在同源分子
	CrPxt	介导细胞-细胞，细胞-细胞外基质之间的黏附	-	-	不存在同源分子
	CrPtx-like	参与体液免疫	C反应蛋白	参与固有免疫反应	同源
	补体系统分子C3、CFB、MASP等	调理作用、炎症反应	补体系统分子C3、CFB、MASP等	调理作用、炎症反应、溶解细胞	同源
细胞因子 Cytokine	TNF-α	参与细菌的免疫反应	TNF-α	识别病原体，激活NF-κB	同源
	IL-17	介导抗真菌和细菌的保护性免疫	IL-17	介导抗真菌和细菌的保护性免疫，也与多种自身免疫性和慢性炎症性疾病相关	同源
	CiTGF-β	参与免疫应答，激活免疫细胞	hTGF-β	调节炎症过程	同源
组织重构与伤口愈合相关因子 Factors related to tissue remodeling and wound healing	MMP-9样分子	胚胎发生、组织重构、血管生成、伤口愈合	MMP-9	胚胎发生、组织重构、血管生成、伤口愈合	同源
	MIF	介导免疫反应	MIF	介导固有免疫和适应性免疫反应	同源
顺式调控元件 Cis-regulatory element	Cr8long、Cr8short	功能尚不明确	RTP	与嗅觉相关	同源
顺式调控元件 Cis-regulatory element	CrCAP	免疫应答调控	GAIT复合物	免疫应答调控	同源
抗菌肽 Antimicrobial peptide	Ci-MAM-A、 Ci-PAP-A	参与初次免疫应答	-	-	不存在同源分子

免疫系统组成 Immune system composition	玻璃海鞘 Ciona intestinalis		人 Homo sapiens		进化差别 Evolutionary difference
免疫系统组成 Immune system composition	分子 Molecules	作用 Function	分子 Molecules	作用 Function	进化差别 Evolutionary difference
免疫识别分子 Immune recognition molecules	TLR	介导免疫应答	TLR	介导免疫应答	人类TLR具有更多亚型
	凝集素	特异性结合糖蛋白	-	-	不存在同源分子
	酚氧化酶	杀死细菌，合成黑色素	-	-	不存在同源分子
	CrPxt	介导细胞-细胞，细胞-细胞外基质之间的黏附	-	-	不存在同源分子
	CrPtx-like	参与体液免疫	C反应蛋白	参与固有免疫反应	同源
	补体系统分子C3、CFB、MASP等	调理作用、炎症反应	补体系统分子C3、CFB、MASP等	调理作用、炎症反应、溶解细胞	同源
细胞因子 Cytokine	TNF-α	参与细菌的免疫反应	TNF-α	识别病原体，激活NF-κB	同源
	IL-17	介导抗真菌和细菌的保护性免疫	IL-17	介导抗真菌和细菌的保护性免疫，也与多种自身免疫性和慢性炎症性疾病相关	同源
	CiTGF-β	参与免疫应答，激活免疫细胞	hTGF-β	调节炎症过程	同源
组织重构与伤口愈合相关因子 Factors related to tissue remodeling and wound healing	MMP-9样分子	胚胎发生、组织重构、血管生成、伤口愈合	MMP-9	胚胎发生、组织重构、血管生成、伤口愈合	同源
	MIF	介导免疫反应	MIF	介导固有免疫和适应性免疫反应	同源
顺式调控元件 Cis-regulatory element	Cr8long、Cr8short	功能尚不明确	RTP	与嗅觉相关	同源
顺式调控元件 Cis-regulatory element	CrCAP	免疫应答调控	GAIT复合物	免疫应答调控	同源
抗菌肽 Antimicrobial peptide	Ci-MAM-A、 Ci-PAP-A	参与初次免疫应答	-	-	不存在同源分子

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[2]	SUN Han, GUO Peng, YU Xinhe, ZHANG Junqiao, YAO Ying, YANG Wen. Progress in Caenorhabditis elegans as a Degenerative Disease Model for Molecular Pathways Studying [J]. Laboratory Animal and Comparative Medicine, 2025, 45(6): 738-751.
[3]	YANG Rong, ZHAO Yining, YANG Wenjing, ZHAO Shanming, CHAI Yujing, ZHANG Chengcai, YUAN Zheng, CUI Shufang. Effect of ⁶⁰Co γ-ray Radiation on Spleen of Naked Mole Rats [J]. Laboratory Animal and Comparative Medicine, 2020, 40(6): 519-522.
[4]	CHEN Chao, CONG Wei, YANG Wen-jing, CUI Shu-fang. Comparative Study on Radiation Resistance of Naked Mole-rat and Mice [J]. Laboratory Animal and Comparative Medicine, 2019, 39(6): 479-483.
[5]	ZHU Xiao-su，SONG yan，XU Shi-qmg . Application of Bombyx mori as Model Organism in Modern Biology [J]. Laboratory Animal and Comparative Medicine, 2009, 29(1): 61-65.
[6]	LI Jun, XU Shu-yun. Some Progress of Intact Animal Model in Antiinflammatory-immunomodulating Pharmacology [J]. Laboratory Animal and Comparative Medicine, 2002, 22(3): 162-167.