472
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wileyonlinelibrary.com/journal/jai J Appl Ichthyol. 2018;34:472–480.
© 2018 Blackwell Verlag GmbH
1 | INTRODUCTION
In 2008, a new vitamin K-dependent protein was identified and
entitled Gla-rich protein (GRP, also known as UCMA – Upper zone of
growth plate and Cartilage Matrix Associated protein) due to its high
Gla content in the mature form. This protein was first identified and
isolated from sturgeon by our group and found to have orthologs in
all taxonomic groups of vertebrates and a paralog (Grp2, also known
as Ucmaa) in bony fish (Fazenda, Silva, Cancela, & Conceição, 2012;
Viegas et al., 2008).
Initially, GRP was described as being specific to cartilage
(Surmann-Schmitt et al., 2008; Tagariello et al., 2008), but also since
been detected in blood cells, skin, vascular system, and in osteo-
cytes of bone, being also associated to ectopic calcifications in dif-
ferent human pathologies (Viegas et al., 2009). In addition to the
presence of Gla residues, no other identifiable functional domains
were described. The association of this protein with high affinity
calcium binding (Viegas et al., 2008) and accumulation at sites of
pathological calcification (Viegas et al., 2009) suggests that GRP
may function as a modulator of calcium availability. Additionally, its
association with fibrillary collagens type II, V, IX, and XI, but not type
I collagen, also suggests that GRP may be involved in the organiza-
tion and/or stabilization of cartilage matrix and may play a key role
in chondrogenesis (revised in Cancela, Conceição, & Laizé, 2012).
Based on its negative action in the differentiation of preosteoblast
MC3T3-E1 cell line and murine primary calvaria cells, GRP has been
proposed as functioning as an inhibitor of osteogenesis (Surmann-
Schmitt et al., 2008). Considering the many studies available, GRP
might have a physiological role in cartilage development and calci-
fication during skeleton formation (revised in Cancela et al., 2012).
However, no clear results are available to date concerning its func-
tion. While in mice the knockout did not appear to have a specific
phenotype (Eitzinger et al., 2012), the morpholino-mediated knock-
down of grp1 (also known as ucmab) in zebrafish showed a weak and
transient phenotype affecting cartilage development (slight overall
growth retardation, smaller head, reduced eye pigmentation, irreg-
ular and undulating notochord), but also severe and definitive phe-
notypes where morphants lacked craniofacial cartilage in almost all
cases and with their notochord strongly spirally compressed (Neacsu
et al., 2011). Due to the apparent differences between mouse GRP
Received: 19 January 2016
|
Accepted: 2 August 2017
DOI: 10.1111/jai.13662
ORIGINAL ARTICLE
Generation of zebrafish Danio rerio (Hamilton, 1822) transgenic
lines overexpressing a heat-shock mediated Gla-rich protein
C. Fazenda
1,2
| G. Martins
1
| P. J. Gavaia
1,3
| M. L. Cancela
1,3,4
| N. Conceição
1,3,4
1
Centre of Marine Sciences (CCMAR),
University of Algarve, Faro, Portugal
2
PhD program in Biomedical Sciences,
Department of Biomedical Sciences and
Medicine, University of Algarve, Faro,
Portugal
3
Department of Biomedical Sciences and
Medicine, University of Algarve, Faro, Portugal
4
Algarve Biomedical Center, University of
Algarve, Faro, Portugal
Correspondence
Natércia Conceição, Departamento
de Ciências Biomédicas e Medicina,
Universidade do Algarve, Faro, Portugal.
Email: nconcei@ualg.pt
Funding information
FCT - Foundation for Science and
Technology through project UID/
Multi/04326/2013, Grant/Award Number:
SFRH/BD/66745/2009 and SFRH/
BPD/111898/2015
Summary
In an effort to provide more information on the function of Grp isoforms in zebrafish,
two zebrafish transgenic lines were generated that could conditionally overexpress
grp genes. Reported here is the process and strategy used for the generation of these
transgenic lines. Overexpression of Grp1 and Grp2 were induced by heat-shock
treatment to investigate their possible roles in the skeleton development. Differences
in skeleton development were analysed by alizarin red staining in the larvae. Although
no differences in total deformities between wild type and Grp overexpressing larvae
were observed, Grp1 and Grp2 overexpressing larvae presented a high percentage of
deformities in abdominal and caudal fin vertebra, respectively, with a suggested spe-
cific localization of deformities for each isoform.