The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The requested identity is verified. elna—also historically called eln1—is a Danio rerio gene encoding Elastin a, a secreted tropoelastin precursor in the elastin family. It is not the distinct zebrafish paralog elnb/eln2. The strongest functional interpretation is that Elna is a non-enzymatic extracellular-matrix structural protein whose mature, cross-linked product supplies reversible extensibility and elastic recoil, particularly to cardiac valves and cardiovascular elastic fibers. Direct mutant evidence indicates that Elna is dispensable for gross embryonic viability but important for long-term valve architecture, cardiac integrity, and survival.
The zebrafish literature must be interpreted carefully because many histochemical and antibody assays detect total elastin without distinguishing Elna from Elnb. Elnb is the dominant elastin paralog in the bulbus arteriosus and has a specialized role in its smooth-muscle fate and elasticity; those Elnb-specific findings should not be assigned to Elna. (hoareau2022zebrafishasa pages 8-9, moriyama2016evolutionofthe pages 4-4)
| Annotation topic | Best-supported conclusion | Evidence type | Confidence / caveat |
|---|---|---|---|
| Identity | Danio rerio elna, also called eln1, encodes Elastin a/tropoelastin and corresponds to UniProt A0A8N1TQS2. It is distinct from the teleost paralog elnb/eln2. Elna is on chromosome 15 and is more similar to human ELN than Elnb: approximately 37% identity and 41% similarity versus 18% and 21% for Elnb. (hoareau2022zebrafishasa pages 2-4) | Zebrafish comparative genomics, synteny, and sequence analysis | High. Multiple zebrafish-specific sources agree; findings for elnb must not be assigned to elna. |
| Protein class and extracellular maturation | Elna is a secreted tropoelastin precursor in the elastin family, with alternating hydrophobic and lysine-rich cross-linking regions and a conserved cysteine-containing C terminus. By established elastin biology, tropoelastin is deposited on fibrillin-rich microfibrils and covalently cross-linked by lysyl oxidases into insoluble elastic fibers. (hoareau2022zebrafishasa pages 2-4, bhanji2007elastininzebrafisha pages 23-29) | Elna sequence/domain comparison plus established elastin-family biochemistry | High for protein-family architecture; moderate for the detailed zebrafish-Elna maturation mechanism because direct paralog-specific secretion and cross-linking assays are limited. |
| Principal localization | The mature product functions outside cells in the extracellular matrix, principally within elastic fibers of cardiovascular structures. Zebrafish elastin occurs in the bulbus arteriosus, atrioventricular and ventriculo-bulbar valves, and arterial elastic lamellae. Mutant evidence indicates that valves preferentially depend on Elna, whereas Elnb remains prominent in vessels and the bulbus arteriosus. (hoareau2022zebrafishasa pages 9-11, hoareau2023characterizationofthe pages 13-14) | Histological orcein staining, elastin immunohistochemistry, and mutant comparison | Moderate–high. Histological reagents generally detect elastin and may not distinguish Elna from Elnb; valve depletion in elna mutants provides stronger Elna-specific localization evidence. |
| Primary mechanical function | Elna contributes to elastic-fiber resilience, reversible extension, and recoil during repetitive cardiovascular loading. Together with collagen and microfibrils, elastin helps smooth pulsatile flow and maintain valve and vessel-wall integrity; zebrafish vascular elastic lamellae decline from about 8–10 near the bulbus exit to 4–5 in the ventral aorta and 1–2 in the dorsal aorta. (hoareau2022zebrafishasa pages 9-11) | Histology, comparative vascular mechanics, and elastin-family functional inference | High for elastin’s structural role; moderate for Elna’s precise share because both paralogs contribute in some cardiovascular sites. Elna is structural, not an enzyme or transporter. |
| Developmental expression | elna/eln1 expression is detected near the cardiac outflow tract and bulbus arteriosus at approximately 3 days post-fertilization. At 3 dpf, both elna and elnb are expressed in the outflow tract, but elnb is stronger; by 4 dpf, elnb also exceeds elna in the bulbus and swim bladder. (bhanji2007elastininzebrafish pages 23-29, faucherre2020piezo1isrequired pages 6-9) | Whole-mount in situ hybridization and quantitative RT-PCR | High for spatial and temporal expression; reported comparisons are largely relative rather than absolute. |
| Direct loss-of-function evidence | The elnasa12235 T→A nonsense allele converts Tyr88 to a stop codon, predicting an 87-residue product likely subject to degradation. Embryonic development and 7-dpf heart rate were grossly normal, but adult mutants developed premature, incompletely penetrant valve disease and reduced survival. By 20 months, mortality was 56% in heterozygotes and 53% in homozygotes versus 12% in wild type; some hearts were 4–5 times normal size. At 12 months, abnormal valve organization affected more than 50% of mutants versus none of the wild types, and honeycomb-like valve areas approached 60% versus no more than 20% in wild type. (hoareau2023characterizationofthe pages 6-12, hoareau2023characterizationofthe pages 4-6) | Direct germline mutant, longitudinal survival analysis, cardiac histology, and heart-rate measurement | High for delayed adult pathology and survival effect. Valve histology used only four fish per genotype and some measurements lacked statistical power; heterogeneity and residual Elnb complicate dosage interpretation. |
| Piezo1/hemodynamic regulation | Cyclic blood-flow forces are sensed by endothelial Piezo1b in the outflow tract. Loss of Piezo1b disrupts outflow-tract development and reduces expression of both elna and elnb at 3 dpf, placing Elna-associated matrix production downstream of mechanosensation. The outflow tract undergoes much greater cyclic deformation than the dorsal aorta—approximately 16.87 ± 0.24 μm at systole versus a 0.72 ± 0.20 μm systolic increase, respectively. (faucherre2020piezo1isrequired pages 6-9, faucherre2020piezo1isrequired pages 20-23) | Knockdown, channel inhibition, rescue, endothelial electrophysiology, in situ hybridization, and live morphometry | Moderate–high. Direct evidence links Piezo1b to elna expression, but the complete intermediates between mechanosensation and elna transcription remain unresolved and effects are not Elna-exclusive. |
| Translational application | The elnasa12235 line is a zebrafish model for elastin insufficiency and age-progressive cardiac-valve pathology. Its delayed, viable phenotype supports longitudinal imaging, modifier studies, and comparatively scalable testing of candidate therapies for elastinopathy and valve degeneration. (hoareau2023characterizationofthe pages 1-2, hoareau2023characterizationofthe pages 14-16) | Disease-model characterization and expert interpretation | Moderate. The model is preclinical, exhibits incomplete penetrance, and does not fully reproduce single-copy human ELN biology because zebrafish retain elnb. |
Table: This table summarizes the identity, extracellular structural function, localization, regulation, mutant phenotype, and translational relevance of Danio rerio elna. It distinguishes direct Elna-specific findings from evidence inferred from Elnb or general elastin biology.
The literature confirms that zebrafish possess two teleost-duplication-derived elastin genes, elna/eln1 and elnb/eln2, encoding distinct tropoelastins. Thus, the supplied annotation—A0A8N1TQS2, Elastin/Tropoelastin precursor, gene elna, organism Danio rerio—is internally consistent. Elna lies on chromosome 15, whereas elnb lies on chromosome 21. Predicted Elna is approximately 101 kDa and encoded by 57 exons; Elnb is approximately 173 kDa and encoded by 59 exons. Elna is the more human-ELN-like paralog, with approximately 37% amino-acid identity and 41% similarity to human tropoelastin, compared with about 18% identity and 21% similarity for Elnb. (hoareau2022zebrafishasa pages 2-4)
This assignment also agrees with the supplied InterPro designation Tropoelastin, IPR003979. No evidence encountered indicated that zebrafish elna denotes an unrelated protein. Results concerning similarly named genes in other organisms were therefore excluded.
Elna is not an enzyme, transporter, receptor, or conventional soluble signal. Its primary function is mechanical and structural. Like other vertebrate tropoelastins, it contains alternating hydrophobic and lysine-rich cross-linking regions. Hydrophobic regions support association and elastomeric behavior; lysine-containing regions enable covalent cross-link formation. Its conserved C terminus includes a tetrabasic interaction motif and paired cysteines that form a disulfide bond important for elastic-fiber assembly. (hoareau2022zebrafishasa pages 2-4)
The accepted elastogenesis model is that soluble tropoelastin is secreted, associates with a fibrillin-rich microfibrillar scaffold and accessory proteins such as fibulins and EMILINs, and is covalently cross-linked by lysyl oxidases to form insoluble elastin. The resulting elastic fiber has an elastin-rich core surrounded by fibrillin-rich microfibrils. For zebrafish Elna, the family membership and sequence architecture strongly support this mechanism, although direct paralog-specific secretion and biochemical cross-linking experiments remain limited. (bhanji2007elastininzebrafisha pages 23-29, hoareau2022zebrafishasa pages 1-2)
Functionally, the cross-linked polymer stores energy during tissue deformation and releases it during recoil. In the cardiovascular system this helps valves and vessel walls endure repetitive loading, maintain structural integrity, and smooth pulsatile flow. Collagen provides complementary resistance to overextension and rupture. Elna should therefore be annotated as an extracellular elastic-fiber structural constituent contributing to tissue resilience and recoil. (hoareau2022zebrafishasa pages 9-11, hoareau2022zebrafishasa pages 1-2)
The functional product acts outside the cell, in the extracellular matrix. Tropoelastin is the soluble precursor; mature elastin is an insoluble, covalently cross-linked elastic-fiber component. It is therefore inappropriate to describe Elna's principal action as cytoplasmic or nuclear.
Zebrafish elastin is detected histologically in the bulbus arteriosus, atrioventricular valve, ventriculo-bulbar valve, and arterial elastic lamellae. Elastic lamellae alternate with vascular smooth-muscle layers. Their abundance decreases with distance from the heart: approximately 8–10 lamellae occur near the bulbus exit, 4–5 in the ventral aorta, and 1–2 in the dorsal aorta. (hoareau2022zebrafishasa pages 9-11)
These measurements establish total elastin distribution but are not wholly paralog-specific. Antibodies raised against mammalian tropoelastin may preferentially recognize one zebrafish paralog, while orcein stains mature elastic material rather than a specific gene product. The strongest Elna-specific localization inference comes from the elna mutant: elastin is markedly depleted and valve architecture disrupted, whereas residual elastin in vessels and the bulbus arteriosus is plausibly supplied by Elnb. The 2023 authors consequently proposed that cardiac valves preferentially depend on Elna, while Elnb provides partial compensation elsewhere. (hoareau2023characterizationofthe pages 12-13, hoareau2023characterizationofthe pages 13-14)
Whole-mount in situ hybridization and quantitative RT-PCR detected eln1/elna expression near the cardiac outflow tract and bulbus arteriosus at approximately 3 days post-fertilization. At 3 dpf, both elna and elnb are expressed in the outflow tract, but elnb expression is stronger; by 4 dpf, elnb also exceeds elna in the bulbus arteriosus and swim bladder. (bhanji2007elastininzebrafish pages 23-29, bhanji2007elastininzebrafisha pages 23-29, faucherre2020piezo1isrequired pages 6-9)
The paralogs are therefore not simply redundant copies. Elna retains greater sequence resemblance to tetrapod ELN and is especially important for adult valve integrity. Elnb has undergone stronger teleost-specific specialization: it is the major bulbar elastin and helps direct cardiac precursor cells toward smooth-muscle rather than cardiomyocyte fate. Elna knockdown can reduce bulbar deformation, indicating a contribution to mechanics, but elnb disruption has much larger effects on contraction duration, bulbar morphogenesis, and cell identity. Elna RNA also fails to rescue the elnb cell-fate phenotype, demonstrating functional nonequivalence. (hoareau2022zebrafishasa pages 8-9, moriyama2016evolutionofthe pages 4-4)
The most informative recent study is Hoareau et al., published 23 May 2023 in Cells (DOI/URL). The elna^sa12235 allele is a T→A point mutation that replaces Tyr88 with a stop codon, predicting an 87-amino-acid truncation likely to be rapidly degraded. Genotypes followed Mendelian segregation, supporting viability through early development. (hoareau2023characterizationofthe pages 2-4, hoareau2023characterizationofthe pages 4-6)
Embryos showed normal gross development and survival through 7 dpf, and heart rate at 7 dpf was not detectably altered. This argues against an indispensable early contractile or cardiogenic role and is consistent with compensation by Elnb and the delayed consequences of defective extracellular-matrix maintenance. (hoareau2023characterizationofthe pages 6-12, hoareau2023characterizationofthe pages 14-16)
Pathology emerged principally in adults and was heterogeneous and incompletely penetrant:
Valve histology used four fish per genotype and age, and not every valve was evaluable. Some genotype-dependent reductions in elastin staining consequently failed to reach statistical significance. The robust interpretation is therefore that elna deficiency causes age-progressive, variably penetrant valve and cardiac pathology, while exact gene-dosage relationships require larger cohorts. (hoareau2023characterizationofthe pages 12-13, hoareau2023characterizationofthe pages 2-4)
Elna participates in the extracellular elastogenesis program: tropoelastin deposition on fibrillin-rich microfibrils, organization by elastic-fiber-associated proteins, and lysyl-oxidase-mediated cross-linking into mature elastin. Associated matrix proteins include fibrillins, fibulins, EMILINs, MAGPs, latent TGF-β-binding proteins, and ADAMTS-family components. This is a matrix-assembly pathway rather than a metabolic reaction catalyzed by Elna itself. (bhanji2007elastininzebrafisha pages 23-29, hoareau2022zebrafishasa pages 9-11)
Faucherre et al., published June 2020 in the Journal of Molecular and Cellular Cardiology (DOI/URL), place outflow-tract elastin expression downstream of hemodynamic sensing. Endothelial Piezo1b responds to mechanical force; its loss or inhibition abolishes mechanically induced endothelial currents, disrupts outflow-tract maturation, and reduces expression of both elna and elnb at 3 dpf. Mouse PIEZO1 RNA rescues the zebrafish outflow-tract defect, supporting pathway conservation. (faucherre2020piezo1isrequired pages 6-9, faucherre2020piezo1isrequired pages 20-23)
The mechanical stimulus is substantial: outflow-tract diameter changed by about 16.87 ± 0.24 μm during systole, compared with only a 0.72 ± 0.20 μm systolic increase in the dorsal aorta. The supported pathway is therefore:
cardiac contraction/blood flow → endothelial Piezo1b activation → downstream mechanotransductive signaling → elna/elnb expression and elastic outflow-tract maturation.
The intermediate transcriptional mechanism remains unresolved, and this pathway is not Elna-exclusive. (faucherre2020piezo1isrequired pages 6-9)
Latent TGF-β-binding protein 3 is required for proper Elnb-associated bulbar development but does not alter elnb transcript abundance, suggesting a role in extracellular maturation rather than gene production. Valve regeneration also involves TGF-β signaling. These observations establish relevant elastic-matrix context but should not be represented as direct proof of Elna-specific TGF-β regulation. (hoareau2022zebrafishasa pages 8-9, moriyama2016evolutionofthe pages 4-4)
The principal real-world application is as a zebrafish model of elastin insufficiency and age-progressive cardiac-valve disease. Human ELN insufficiency causes disorders including supravalvular aortic stenosis and Williams–Beuren syndrome, while other ELN variants cause cutis laxa. Because elna^sa12235 fish survive embryogenesis yet develop premature adult pathology, the line is suitable for longitudinal imaging, genetic-modifier studies, extracellular-matrix research, and relatively scalable testing of candidate interventions. The transparent embryo, high fecundity, and availability of CRISPR and fluorescent reporters strengthen this use case. (hoareau2022zebrafishasa pages 1-2, hoareau2023characterizationofthe pages 1-2)
The 2023 investigators argue that zebrafish can accelerate therapeutic screening and reduce mammalian-animal use, rather than replace mammalian models. That caution is warranted: zebrafish retain the compensating elnb paralog, their bulbus arteriosus has no exact adult mammalian counterpart, and the mutant phenotype is heterogeneous. (hoareau2023characterizationofthe pages 13-14, hoareau2023characterizationofthe pages 14-16)
The most recent gene-specific functional advance in the retrieved 2023–2024 literature is the 2023 characterization of elna^sa12235, which shifted the annotation from sequence/expression inference toward direct evidence for adult valve maintenance and survival. A 2024 review of duplicated zebrafish genes emphasized that teleost paralogs commonly develop distinct functions and should be studied together, an interpretive principle strongly applicable to elna/elnb; however, it added little direct Elna-specific experimentation.
Important unresolved questions are:
Danio rerio elna encodes a secreted tropoelastin precursor that is assembled and cross-linked in the extracellular matrix into elastic fibers. Its principal molecular role is to provide reversible extensibility, recoil, and long-term mechanical integrity, particularly in cardiac valves and cardiovascular tissues. Expression in the developing outflow tract is responsive to Piezo1-dependent hemodynamic mechanotransduction. Direct loss-of-function evidence shows that Elna is not essential for gross embryonic development but is required for normal adult valve organization, cardiac homeostasis, and lifespan. Functional attribution must remain distinct from elnb, the more specialized and predominant bulbus-arteriosus paralog.
References
(hoareau2022zebrafishasa pages 8-9): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Zebrafish as a model to study vascular elastic fibers and associated pathologies. International Journal of Molecular Sciences, 23:2102, Feb 2022. URL: https://doi.org/10.3390/ijms23042102, doi:10.3390/ijms23042102. This article has 38 citations.
(moriyama2016evolutionofthe pages 4-4): Yuuta Moriyama, Fumihiro Ito, Hiroyuki Takeda, Tohru Yano, Masataka Okabe, Shigehiro Kuraku, Fred W. Keeley, and Kazuko Koshiba-Takeuchi. Evolution of the fish heart by sub/neofunctionalization of an elastin gene. Nature Communications, Jan 2016. URL: https://doi.org/10.1038/ncomms10397, doi:10.1038/ncomms10397. This article has 109 citations and is from a highest quality peer-reviewed journal.
(hoareau2022zebrafishasa pages 2-4): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Zebrafish as a model to study vascular elastic fibers and associated pathologies. International Journal of Molecular Sciences, 23:2102, Feb 2022. URL: https://doi.org/10.3390/ijms23042102, doi:10.3390/ijms23042102. This article has 38 citations.
(bhanji2007elastininzebrafisha pages 23-29): T Bhanji. Elastin in zebrafish and mice. Unknown journal, 2007.
(hoareau2022zebrafishasa pages 9-11): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Zebrafish as a model to study vascular elastic fibers and associated pathologies. International Journal of Molecular Sciences, 23:2102, Feb 2022. URL: https://doi.org/10.3390/ijms23042102, doi:10.3390/ijms23042102. This article has 38 citations.
(hoareau2023characterizationofthe pages 13-14): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(bhanji2007elastininzebrafish pages 23-29): T Bhanji. Elastin in zebrafish and mice. Unknown journal, 2007.
(faucherre2020piezo1isrequired pages 6-9): Adèle Faucherre, Hamid Moha ou Maati, Nathalie Nasr, Amélie Pinard, Alexis Theron, Gaëlle Odelin, Jean-Pierre Desvignes, David Salgado, Gwenaëlle Collod-Béroud, Jean-François Avierinos, Guillaume Lebon, Stéphane Zaffran, and Chris Jopling. Piezo1 is required for outflow tract and aortic valve development. Jun 2020. URL: https://doi.org/10.1016/j.yjmcc.2020.03.013, doi:10.1016/j.yjmcc.2020.03.013. This article has 90 citations and is from a domain leading peer-reviewed journal.
(hoareau2023characterizationofthe pages 6-12): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(hoareau2023characterizationofthe pages 4-6): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(faucherre2020piezo1isrequired pages 20-23): Adèle Faucherre, Hamid Moha ou Maati, Nathalie Nasr, Amélie Pinard, Alexis Theron, Gaëlle Odelin, Jean-Pierre Desvignes, David Salgado, Gwenaëlle Collod-Béroud, Jean-François Avierinos, Guillaume Lebon, Stéphane Zaffran, and Chris Jopling. Piezo1 is required for outflow tract and aortic valve development. Jun 2020. URL: https://doi.org/10.1016/j.yjmcc.2020.03.013, doi:10.1016/j.yjmcc.2020.03.013. This article has 90 citations and is from a domain leading peer-reviewed journal.
(hoareau2023characterizationofthe pages 1-2): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(hoareau2023characterizationofthe pages 14-16): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(hoareau2022zebrafishasa pages 1-2): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Zebrafish as a model to study vascular elastic fibers and associated pathologies. International Journal of Molecular Sciences, 23:2102, Feb 2022. URL: https://doi.org/10.3390/ijms23042102, doi:10.3390/ijms23042102. This article has 38 citations.
(hoareau2023characterizationofthe pages 12-13): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.
(hoareau2023characterizationofthe pages 2-4): Marie Hoareau, Naïma El Kholti, Romain Debret, and Elise Lambert. Characterization of the zebrafish elastin a (elnasa12235) mutant: a new model of elastinopathy leading to heart valve defects. Cells, 12:1436, May 2023. URL: https://doi.org/10.3390/cells12101436, doi:10.3390/cells12101436. This article has 7 citations.