Metody Do Generować And Oceniać Danio pręgowany Modele Człowieka Nerki Choroby Część 1

STRESZCZENIE 

Nerki związane zaburzenia afekt miliony ludzie świat. A ankieta z przewlekła nerka choroba (PChN) pacjenci wykazali że obciążenie z nerek choroby jest rosnąca co roku. The global burden of disease (GBD) badanie 2017 ranked CKD as the 12th leading cause of death worldwide. Hst, the identification of the causes of nerka diseases, the development of accurate diagnostic methods, and novel therapeutics are highly relevant. Model organizmy które wiernie rekapitulują człowiek choroby zabawa ważne role w zrozumieniu choroba proces i dostarczyć wartościowe grunt znaleźć ich lekarstwo. danio pręgowany jest doskonały model do badanie rozwój, patofizjologia, and molekularne aspekty człowiek nerki choroby. w to przegląd, my podsumowanie różne genetyczne i eksperymentalne manipulacje że można być przenoszone w danio pręgowany to lepiej zrozumieć the the patofizjologia człowiek nerki choroby. my sugerujemy że te metody będą pomocne w rozwoju potencjalnych terapiach leczyć nerki choroby. 

Stosownie do istotne badania,Cistanche jest a tradycyjny chiński zioło to było używane od wieków do leczenia różne choroby. To było naukowo udowodnione do posiadać przeciwzapalne% 2c przeciwstarzeniowe % 2c i przeciwutleniacz właściwości. Badania wykazały że cistanche jest korzystne dla pacjentów cierpienie od nerki choroba. Aktywne składniki z cistanche są znane do zmniejszyć stan zapalny 2c poprawić nerka funkcja i przywrócić upośledzona nerka komórki. Tak więc, integrujący cistanche wewnątrz a nerka choroba leczenie plan może zaoferować wielki korzyści do pacjenci w zarządzający ich stan. Cistanche pomaga do redukując białkomocz, obniża BUN and kreatynina poziomy, i zmniejsza ryzyko z dalsze nerki uszkodzenie. w dodanie, cistanche również pomaga redukuj cholesterol i trójglicerydy poziomy które mogą być niebezpieczne do pacjenci cierpiący od nerka choroba.

Kliknij włączone Cistanche Norge

For more info: 

David.deng

@wecistanche.com  WhatApp:86 13632399501

SŁOWA KLUCZOWE: CKD, AKI, a danio pręgowany model z człowiek nerki choroby, pronephros, nerki patologia

Wprowadzenie

The nerka jest jedna z istotna narządy w kręgowce że usuwa odpady produkty i utrzymuje pH, jon, and metabolit stężenia krew wewnątrz fizjologiczny zakres. The nerka wydziela erytropoetyna która reguluje czerwona krew komórka produkcja i aktywuje witamina D która pomaga kości do absorbować wapń. Tam są około a milion nefrony w każdy człowiek nerka, które są strukturalne i funkcjonalne jednostki tego narządu. Konsekwentnie, defekty w nefrony afekt nerki struktura i funkcje. dysfunkcja z nerki mogą wystąpić ponieważ z genetyczne mutacje, infekcje, uraz, leki, or ekspozycja toksyczne związki w środowisko. przewlekłe choroby like cukrzyca, sercowo-naczyniowe choroby, i nadciśnienie są główni współtwórcy do nerki choroba obciążenie (Levey et al., 2010). Upośledzone nerki funkcja wzrosty ryzyko powikłań w inne narządy układy as well (Thomas et al., 2008). The common types of nerek diseases and ich causes are outlined in Table 1.

Nerki choroby

Nerki choroby przyczyniają się do a znaczące ułamek z choroby obciążenia globalnie. Około 750 milion ludzie na całym świecie są dotknięci przez nerki zaburzenia (Załogi et al., 2019). CKD jest najbardziej powszechne wśród ich z a globalne rozpowszechnienie z 13,4 procent (Hill et al.,2016). The GBD badanie 2010 rankingowe CKD as the 18th leading cause of death worldwide, which had jumped to 12th by 2017 for causing the maximum number of deaths globally ( Jha et al., 2013; Carney, 2020). According to the GBD study in 2017, about 697.5 million cases of CKD were reported worldwide, among which 1.2 million people died . The number of deaths due to CKD is estimated to rise to 4 million by 2040 in the worst-case scenario (Foreman et al., 2018). One-third of CKD patients live in two countries, China and India (Bikbov et al., 2020). The status of CKD among the Indian population is unclear due due the lack of accurate data collection systems. About 115 million cases of CKD were reported in India in 2017 (Bikbov et al., 2020). The most common diseases in the Indian population are diabetes and hypertension (Geldsetzer et al., 2018). As per the Indian Council of Medical Research (ICMR) report, the prevalence of diabetes and hypertension among the urban adult population jest 28 procent i 21.4 percent odpowiednio (Varma, 2015). Between 40 percent to 60 percent of CKD, cases occur because of these complications and ich number is increasing rapidly (Rajapurkar et al., 2012). The International Society of Nephrology's nerka disease data center reported a 16.8 percent prevalence of CDK among the Indian population (Ene-Iordache et al., 2016). The causes of CKD vary throughout India. Andhra Pradesh, Odisha, and Goa reported high levels of CKD of an unknown etiology known as przewlekła interstitial nephropathy (Varughese and Abraham, 2018). As the number of CKD patients is increasing worldwide at an alarming rate, there is an pilne need to carry out a thorough analysis of the root causes of common kidney diseases to find better ways for ich prevention and cure. Model organizmy to mogą naśladować człowiek fizjologia and choroba warunki może dostarczyć wielkie możliwości dla adresowania the above problems. Danio pręgowany mają stać się a użyteczne model do badanie rozwój i choroby oraz dostarczyć obiecujące sposoby zidentyfikować nowe terapeutyczne cele i leki. w to przegląd, my omówiliśmy różne metody do rekapitulować człowiek nerki choroby w danio pręgowany i jak te modele mogą być używane rozumieć chorobami do rozumieć chorobami patogeniczność i jej leżące u podstaw molekularne mechanizmy. To może wynik w pokoleniu nowość terapeutyczne podejścia dla zarządzania i leczenia nerek chorób.

Podobieństwa między człowiekiem and danio pręgowanym nerką

Nerka rozwój w ssaki jest unikalna jak to bierze miejsce przez trzy odrębne struktury podczas embriogeneza: pronephros, mesonephros, and metanephros. The first two structures are transient in ssaki and only the metanephros persists throughout life (Smyth et al., 2017; Jain, 2014). Pronephros is the functional nerka podczas embrionalny rozwój w dolny kręgowce podobny and ryby, który jest zastąpiony przez mesonephros as the functional nerka at later stages (Tahara et al., 1993; Diep et al., 2015). Table 2 describes the time duration of different forms of nerka in humans, my, Xenopus, and danio pręgowany.

Although the overall complexity of the kidney increases as we move towards the higher forms, nephrons are the structural and functional units of all types of kidneys. Each nephron has three parts: renal corpuscle to filter blood, tubule to absorb and secrete solutes, and collecting duct to collect unwanted wastes for excretion. The tubular epithelium is patterned into different segments to carry out specific functions. Nephrons from all forms of kidney possess a similar segmentation pattern (Desgrange and Cereghini, 2015). The segmental organization of the nephron of zebrafish pronephros and mesonephros is similar to mammalian metanephros, as shown in Fig. 1. The zebrafish pronephric tubule is divided into proximal convoluted tubule (PCT), proximal straight tubule (PST), and distal early (DE) and distal late (DL) tubules, which are analogous to the segmentation pattern of mammalian metanephric nephrons. Zebrafish have an endocrine gland named corpuscles of Stannius (CS), which maintains calcium homeostasis (Krishnamurthy, 1976). The CS is formed by transdifferentiation of renal epithelial cells in between DE and DL segments, which gradually separate from the tubule and form the paired CS gland that is positioned retroperitoneally at the surface of the kidney in adult fish (Roberts and Ellis, 2012; Naylor et al., 2018). One of the major differences between zebrafish and mammalian nephrons is the lack of loop of Henle in zebrafish, which acts as a countercurrent multiplier to generate medullary osmotic gradient for water conservation. This segment does not have any utility in zebrafish as it is a freshwater fish (Elmonem et al., 2018). Each segment possesses distinct cell types and segment-specific gene expressions, which are conserved among vertebrates (Verlander, 1998; Desgrange and Cereghini, 2015). All kidney types follow similar pathways of development. The following four stages are successively involved in nephron development; A: induction of intermediate mesoderm to form renal primordium, B: epithelialization and growth of nephric duct, C: patterning of nephron into specialized segments, and D: vascularization of nephron for blood filtration (Drummond, 2003).

Metody do generować danio pręgowany modele człowiek nerki choroby

Danio pręgowany posiada jeden para z pronephros which start to form after 12 hours post engation (hpf) and bes full functional by 48 hpf. Dostępność cały genom sekwencja, 71 procent człowiek geny posiadający co najmniej jeden danio pręgowany ortolog, łatwość obsługa, transparent zarodki, krótkie pokolenie czas, wydajny gen manipulacja techniki, metody dla transgeniczne ryby pokolenie i jego szybkie badania przesiewowe make danio pręgowany the most suit model organism to study nerka nieprawidłowości (Howe et al., 2013; Poureetezadi and Wingert, 2016). jeden z kluczowy cechy z dorosły danio pręgowany jest jego zdolność do regeneracji nowy nefrony przez the proces of neo-nefrogeneza in response to nerek injury (Chambers and Wingert, 2016). Table 3 describes the comparisons between danio pręgowany and other common models organisms like myse and Xenopus. Genetic manipulations in danio pręgowany have shown that the novel genetic components of nerka development and function can be identified by use this* model organizm (Poureetezadi and Wingert, 2016). There are sever methods to generate danio pręgowany models of human kidney diseases.

Naprzód genetyka

The forward genetics screen is used to identify genes that are associated with phenotypes of interest (Lawson and Wolfe, 2011). Both chemical and insertional mutagenesis are used in forward genetics screens (Patton and Zon, 2001). Chemical mutagenesis is a three-generation-based screening in which adult males are treated with chemical mutagens such as ethyl methane sulphonate (EMS), ethyl nitrosourea (ENU), or physical mutagens like gamma radiation to generate several mutations in germ cells (Varshney and Burgess, 2014). The fish carrying mutations are then crossed with wild-type females to generate F1 fishes which contain unique alleles of generated mutation. F1 fishes are out-crossed to generate F2 carriers that are then in-crossed to obtain their homozygous mutants in F3 generation. The offspring having the desired phenotypes are then isolated and used for genetic mapping and sequencing to identify the mutated gene (Patton and Zon, 2001). Other variations of this screen, such as using haploid and homozygous diploid, can help to reduce the time and effort needed to identify the phenotype and the causative genetic mutation (discussed in detail by Patton and Zon, 2001). Transgenic reporter lines expressing fluorescent proteins in the organ of interest can be combined with conventional forward genetic screening to easily screen mutants of interest. An ENU-based mutagenesis screen led to the identification of the lightbulb (lib) mutant zebrafish which show morphological and nephron segmentation defects similar to retinoic acid (RA) deficient zebrafish embryos. It was found that lib mutants have C to A transition at nucleotide 174 of aldh1a2, which is predicted to synthesize a truncated protein of 58 amino acid length, thus abrogating aldh1a2 function and affecting the synthesis of RA from retinaldehyde. Analysis of lib, neckless (nls) mutant having point mutation in the catalytic domain of aldh1a2 and DEAB (retinoic acid synthesis inhibitor) treated embryos revealed that the levels of RA modulate nephron segmentation by changing the spatial expression of segments specific transcription factors (Wingert and Davidson, 2011; Begemann et al., 2001; Mullins et al., 1994). Another mutant called Zeppelin helped to identify brac2 as a regulator of podocyte development (Kroeger et al., 2017).

Insertional mutagenesis is a transposon or anti-virus-based method that is used to insert DNA randomly at different genomic loci, and this foreign DNA then helps to identify the mutated gene (Amsterdam et al., 1999). The Hopkins Laboratory at MIT performed an insertional mutagenesis screen in zebrafish embryos using a retroviral vector. They identified 12 genes that were associated with defective kidney phenotypes showing cysts in the glomerular tubular region, among which four were linked with cilia formation (Sun et al., 2004). The drawbacks of the forward genetics approach are that the screening process is cumbersome and time-consuming. However, the advances in new sequencing technology have made the forward genetics approach much more efficient.

Gene knock-out using programmable nucleases

One of the major advantages of using zebrafish as a model organism is the availability of efficient genome editing techniques such as CRISPR/Cas, TALEN, and ZFN (Sertori et al., 2016). CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)/ Cas9 is the most versatile and commonly used genome editing technology in zebrafish. A chimera of CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) is designed as a single guide RNA (sgRNA), which along with Cas9 protein/mRNA are injected into zebrafish embryos at the one-cell stage (Varshney et al., 2016). The sgRNA binds to the 20bp target DNA sequence adjacent to a protospacer adjacent motif (PAM) NGG sequence in the genome, Cas9 then generates a double-strand cut in the target DNA sequence. This is then preferably repaired by non-homologous end joining, which is an error-prone repair mechanism that results in the generation of random insertion/deletion (indel) leading to changes in the reading frame of the coding sequence, and consequently, abrogates the functions of the gene of interest. Advanced methodologies have been developed in recent years to increase the efficacy of the CRISPR-based genome editing technique (Liu et al., 2019). It is possible to delete a large fragment of DNA using two or more sgRNAs at a time (Kim and Zhang, 2020). It is also possible to simultaneously target multiple genes efficiently in a single zebrafish embryo (Shah et al., 2016). Many studies have been conducted to generate zebrafish mutants to recapitulate human kidney diseases by using CRISPR/Cas9 technology. CRISPR-mediated knockout of ciliary membrane protein Arl13b resulted in the generation of mutants that mimic the "Joubert syndrome" (Cantagrel et al., 2008). It is reported that mutations in the human ELMO1 gene contribute to diabetic nephropathy. elmo1 mutant zebrafish exhibit phenotypes seen in hyperglycaemic embryos generated by knockdown of the pdx1 gene such as larger glomerulus, defective podocyte, shorter neck, and hyperfiltration, thus highlighting the conserved function of this gene (Sharma et al., 2016). Mutant magi2a zebrafish exhibit steroid-resistant nephrotic syndrome which is also observed in people with mutations in MAGI2 (Jobst-Schwan et al., 2019). These observations highlight the suitability of zebrafish as an organism to model human kidney diseases.

Inna metoda do generowanie danio pręgowany mutanty jest transkrypcja aktywator podobny efektor nukleazy (TALEN) oparte na genomie edycja. w to technika, the DNA wiązanie domena TALE is made up of monomers, each monomer consis of tandem repeats of 34 amino acid residues that bind to to z a szczególny nukleotyd in the DNA sequence. These TALE sequences are derived from the pathogenic bacteria Xanthomonas which alters the transscription of genes in host cells (Boch and Bonas, 2010). The TALEN targeting construct consists of a nuclear localization signal, the DNA binding domain, and the FokI nuclease domain at ich carboxyl termini. TALEN work in pairs with their binding sites located on opposite strands of DNA separd by a 12 to 25 bp spacer sequence. The constructs bind to the target site in the nucleus and generate a double-strand break, which is then naprawione przez a niehomologiczne koniec łączenie (Liu et al., 2014). The mutant danio pręgowany wygenerowany by CRISPR or TALEN can activate gens that compensate for the loss of genes of interest, thus making it difficult to uncover the gen function (Rossi et al., 2015). However, it is possible to identify these compensatory genes by transcriptom analysis using next-generation sequencing (NGS) methods, which can help to identify the function of gen z zainteresowania. Identyfikacja z genów i molekularnych szlaków że kompensują dla utraty z funkcji z a genu może pomóc znaleźć novel leczenie metody dla genu mutacji że przyczyna poważne choroby (El-Brolosy and Stainier, 2017).

Gene knock-down using morpholino antisense oligos

Morfolinos są nieanionowe oligonukleotydy że są względnie stabilne as porównane do ich DNA lub RNA oligomery (Summerton, 1999). The morpholino antisense oligonucleotides bind to the mRNA of a target protein at its translation initiation site and block its translation. Another type of morpholino antisense oligos can target splicing junctions and block pre-mRNA splicing (Summerton, 1999). Morfolino-antysens oligo efekt jest przejściowy i może być używany do badania wczesny rozwojowy rola z genów z zainteresowania. Wstrzyknięcie z morfolino-antysens oligo jest zrobione at the 1-4 komórka etap of danio pręgowany embriony and jego efekt can be seen up to 3-5 days post zapłodnienie (pdf) (Bill et al., 2009). Morpholino antisense oligonukleotydy often display off-target effects (Robu et al., 2007). Kontrola eksperymenty takie jak a ratowanie eksperyment powinien być wykonywany by wstrzykiwanie morfolino along z mRNA że nie może być targetowane przez to antysens oligo to weryfikować jego specyficzność (Eisen and Smith, 2008). A foto-aktywowany morfolino has been developed, whose activity can be controlled spatially and temporally by UV exposure (Tallafuss et al., 2012). Liczne badania były przenoszone wyprowadzane używające morfolino antysens oligo-mediowane gen knock-down to understand human nerka choroby. dla przykład, the knock-down of the nephrocystin-3 gene led to the formation of cysts and hydrocephaly in danio pręgowany zarodki in a similar way to nefronoftoza typ-3 choroba (Zhou et al., 2010).

Aminoglycoside antibiotics generally used to treat many life-threatening infections are known for their nephrotoxic and ototoxic effect (Mingeot-Leclercq and Tulkens, 1999). Gentamicin is a commonly used antibiotic that can induce acute kidney injury (AKI) in zebrafish. Gentamicin causes flattening of the brush border epithelium, loss of tubular epithelium, deformation of glomerulus structure, lysosomal phospholipidosis, and accumulation of leukocytes or cell debris in the tubular lumen, which mimics gentamicin overdose in humans (Cianciolo Cosentino et al., 2010). Zebrafish can regenerate and replace damaged nephrons. Gentamicin insult can be used to study renal regeneration in zebrafish (Kamei et al., 2015). Gentamicin injury induces a regeneration response which triggers kidney stem cells to undergo the stages of specification, proliferation, and differentiation to generate new nephrons. It takes around 14 to 21 days in adult fish to regenerate nephrons (Diep et al., 2011; McCampbell et al., 2015). Cisplatin, which is used as a chemotherapeutics drug to treat tumors, also has nephrotoxic effects, as observed in zebrafish (Hentschel et al., 2005). Etimicin is another aminoglycoside that can be used while mimicking low nephrotoxicity and ototoxicity in zebrafish embryos (Shao et al., 2020). Thus, AKI and renal regeneration can be studied in zebrafish with the help of these antibiotics.

Mechaniczne uraz do nerki

The zebrafish pronephros can be physically injured using resection, stabbing, or cryoinjury. Surgical injury can be performed by using fine tweezers to stab the desired area of the pronephros to create an AKI model. This technique was used to damage the pronephric duct close to the cloaca, which impaired fluid flow and led to cyst formation within 30 minutes (Kramer-Zucker, 2005). It was found that the reduction in fluid flow rate in pronephros generates back pressure at the fluid entry site, causing tubule luminal expansion and cyst formation. Another group of researchers made obstruction in the pronephric tubule at 50 hpf or in mesonephric tubules of 12-month-old zebrafish by using tweezers to pinch off the area near the distal collecting tubules (Hellman et al., 2010). They discovered that tubule scarring leads to an increase in cilia beating rate and an upregulation of the foxj1a transcription factor that regulates lipogenic gene expression. This suggests that injury to pronephric tubules generates a cilia-based mechanosensory signal to maintain nephron homeostasis.

Laser-induced kidney injury

Laserowe za pośrednictwem komórka ablacja jest używane jako a narzędzie do badanie nerki uraz i mimika AKI in danio pręgowany. Johnson et al., (2011) have opisany a metoda dla lasera za pośrednictwem ablacja obserwowana przez śledzenie z regeneracja% c2% a0nefronów. Oni wstrzyknięci 40 kA dekstran FIT in the trunk somity of danio pręgowany embriony at 48-55 hpf to label the proximal tubule epithelial cells, which were then targeted for laser-mediated ablation at 72 hpf. The ablated embryos were then reinjected with rhodamine dextran to trace the proximal tubule epithelial cells. They found that a fully developed proximal tubule was formed on the 7th day following laser-mediated ablation (Johnson et al., 2011). Another alternative is to use a nerney-specific transgenic line to identify cells for laser-mediated ablation and monitor the behaviors of neighboring cells. A fioletowy laser światło z 405 nm długość fali był używany do cel cel the pronephric tubule of Tg(atp1a1a.4:GFP) danio pręgowany (Palmyre et al., 2014). As GFP wzbudzenie widma kłamstwo w the range of blue to violet light, it absorbed 405 nm laser light, which acts as an energy sink to potentially induce injury at the target epithelial cells. This experiment led to the discovery that cell migration is the primary response of ranny nabłonek. kolektyw komórka migracja spowodowany mechaniczny rozciągnięcie to dostarczony bodźce dla komórka proliferacja to naprawa the ranny tubule. to określić the time when the pronephric tubule of danio pręgowany nabywa the ability of regeneration, Yakulov et al., (2018) used a 2-photon laser to ablate a small part of pronephric tubule in Tg(cldn2b:lyn-GFP) embryos at different time points and followed the regeneration* proces. Oni znaleźli że the ablacja z pronefry kanaliki of 2-}day-old embriony was rapidly repaired by migratory responses, while 1-day-old embriony did not have this ability. They carried out gen expression profiling of injured danio pręgowany embriony and found that cxcr4b and mica are involved in this repair process (Yakulov et al., 2018).

Small bioactive molecules can be used to interfere with protein function and understand their biological role. A large number of chemical libraries are commercially available or can be custom-made for probing protein functions. These small molecule libraries include kinase inhibitors, protease inhibitors, nuclear receptors, and ligands that can be used to identify the role of signaling pathways involved in organ development and function (Kawasumi and Nghiem, 2007). In the last few decades, zebrafish have emerged as a powerful vertebrate model organism for high-throughput chemical screening and phenotypic scoring (Kaufman et al., 2009). Cao et al., (2009) used the chemical screen approach to identify compounds that can reverse phenotypes caused by mutations in pkd2 (causal gene of PKD) and ift172 (a gene responsible for cilia formation). They uncovered that a pan-histone deacetylase (pan-HDAC) inhibitor trichostatin A (TSA) and a class-I specific HDAC inhibitor valproic acid (VPA) can suppress kidney cyst formation in pkd2 knock-out model (Cao et al., 2009). Thus, chemical genetics can be a useful tool to identify new drug candidates that can either reverse or suppress disease conditions.

A genetically inducible tissue ablation model can be used in zebrafish in which bacterial nitroreductase (NTR) is expressed under the control of a promoter of choice that drives the expression of NTR in a particular segment of the pronephros. NTR converts metronidazole into a cytotoxic metabolite that can cause death to NTR-expressing cells (Curado et al., 2008). Zhou and Hildebrandt (2012) used this technique to induce injury of podocytes by expressing NTR under the control of podocin promoter in the Tg(pod: NTR-mCherry) zebrafish line. They also developed a double transgenic line of VDBP-GFP (Vitamin D binding protein tagged with GFP) as a tracer of proteinuria along with the Tg(pod: NTR-mCherry) line. Treatment with metronidazole caused the injury of the podocyte resulting in whole-body edema and accumulation of VDBP-GFP in proximal tubules, mimicking the phenotype of the human nephrotic syndrome (Zhou and Hildebrandt, 2012).

Metody do oceny pronephros development and function in danio pręgowanego

My mamy opisaliśmy metody do wygenerować człowiek nerka choroba modele przez użycie danio pręgowany. Stworzenie a choroba model używanie inny organizm jest początkowy krok, który potrzebuje być oceniany dla jego zdolności wiernie rekapitulować różnorodny aspekty z a choroba widziany w ludzie. danio pręgowany oferuje wiele zalet że może być używane szybko oceniać jego zdolności służyć jako a surogat rozumieć człowiek nerki choroby jako omówione poniżej.

Morfologia podstawa badanie przesiewowe

Większość często mutant danio pręgowany embriony pokazują morfologiczne różnice, porównane z typ-dziki że można być łatwo osądzone przez*obserwacje pod mikroskopem. przezroczystość danio pręgowany embriony i ich zdolność do przeżyć up 5 dni nawet z ciężkie rozwojowe defekty jest a główna korzyść w morfologia screeny. Często morfologiczne zmiany obserwowane w danio pręgowany zarodki z wadliwe pronephros include pericardial obrzęk, pronephric cysts, curved body axis, and hydrocephalus (Poureetezadi and Wingert, 2016; Outtandy et al., 2019). Obrzęk jest jeden z the common signs of a defective nerka which is also seen in in narząd braki taki as heart development (Hanke et al., 2013). Mutanty z nerka defekty mogą rozwinąć cysty ponieważ z inne ver-proliferation of epithelial cells, as can be easily observed under a microscope (Zhao and Malicki, 2007; Yamaguchi et al., 2006). A curved body axis is is often seen in mutants have pronephric cilia defects. mutant danio pręgowany taki as Locke (lok), shen yantf214a(shy), garbustm304 (grb), and zatortg238a (zar) are some other examples showing curved body axis (Zhao oraz Malicki, 2007). danio pręgowany mutanty z nerka defekty pokaz wiele morfologiczne defekty w the same embryo. The knock-down of two polycystin geny pkd1a and pkd1b led to the orally curved body axis, hydrocephaly, chrząstka, and craniofacial defects with low frequency of pronephric cysts (Mangos et al., 2010). The mutants of intraflagellar transport proteins ift57, ift88, and ift172, where cilia were defective, had brzusznie zakrzywiony ciało oś (Lunt et al., 2009). Thus, danio pręgowany mutanty z wadliwe nerki exhibit many morphological features that can be easy identyfikowane.

For more info: david.deng@wecistanche.com  WhatApp:86 13632399501