Nonketotic hyperglycinemia in captive‐bred Vervet monkeys (<i>Chlorocebus aethiops</i>) with cataracts

Khoza, Sanele; Ngqaneka, Thobile; Magwebu, Zandisiwe E.; Chauke, Chesa G.

doi:10.1111/jmp.12400

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…The PCSK9 gene was amplified by polymerase chain reaction (PCR) using GoTaq® green master mix (Promega). The PCR conditions adopted from 31 consisted of the following steps; 95°C for 5 min, followed by 30 cycles of 95°C for 30 s, 40–70°C for 30 s, and 72°C for 1 min. An extension period of 5 min at 72°C completed the procedure.…”

Section: Methodsmentioning

confidence: 99%

Proprotein convertase subtilisin/kexin type 9 genetic screening using the vervet (Chlorocebus aethiops) model

Ngqaneka

Obikeze

Magwebu

et al. 2022

J of Medical Primatology

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Background The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has come to prominence due to its reported function in the clearance of low‐density lipoprotein cholesterol. The vervet monkey (Chlorocebus aethiops) was utilized to study the genetics of PCSK9 gene. Method Sixteen vervet monkeys were selected to screen for possible PCSK9 polymorphisms and to determine gene expression. Results Four PCSK9 sequence variants (T112T, R148S, H177N and G635G) were identified and three of these variants (H177N, R148S, and G635G) were categorized as loss of function mutations. A decline in gene expression levels was also observed in animals harboring these three variants. Although the selected variants might have affected the level of gene expression in the selected animals, individual variation was also noticed in some of these individuals with the G635G variant. Conclusion Based on the findings obtained from this study, it is suggestive that the activity of PCSK9 was hindered.

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Section: Methodsmentioning

confidence: 99%

Proprotein convertase subtilisin/kexin type 9 genetic screening using the vervet (Chlorocebus aethiops) model

Ngqaneka

Obikeze

Magwebu

et al. 2022

J of Medical Primatology

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“…Each standard PCR reaction (25 μL) consisted of the following reagents: GoTaq PCR Master Mix (2x) (Promega, USA), 2 mmol/L forward and reverse primer, 50 ng μL −1 DNA, and nuclease-free water. The cycling program was similar to the one that has been previously published [26]. Briefly, cycling conditions included denaturation at 94 °C for 5 minutes, followed by 30 cycles at 94 °C for 30 seconds, varying annealing (40-70 °C) for 30 seconds (Table S3), and extension of 72 °C for 1 minute, followed by a final extension of 72 °C for 5 minutes.…”

Section: Candidate Gene Selection and Sequence Retrieval Formentioning

confidence: 99%

The Association between Genetic Variants and Gene Expression in RAAS Genes Using Captive-Bred Vervet Monkeys (Chlorocebus aethiops)

Khoza

Ghai

Chauke

et al. 2023

Advances in Cell and Gene Therapy

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Mendelian genetics contribute largely to the development of hypertension; therefore, the identification of genetic variants related to blood pressure (BP) regulation remains crucial and may reveal new therapeutic drug targets. The purpose of the present study was to screen the captive-bred Vervet colony for salt-sensitive sequence variants or single nucleotide polymorphisms (SNPs) in the selected Renin-Angiotensin-Aldosterone System (RAAS) genes associated with salt sensitivity. Blood samples were collected from 16 captive-bred Vervet monkeys for genotyping and gene expression analysis. The impact of the identified sequence variants was determined using online prediction tools. Sanger sequencing analysis revealed 21 sequence variants in AGT, CYP3A5, GRK4, and SCL4A5, of which 19 were novel and two were previously reported in humans. All novel variants were either predicted to be polymorphic, disease-causing, or possibly damaging by prediction tools. Furthermore, the mRNA expression for AGT was significantly higher in the normal BP group ( p value = 0.02), and a similar trend was observed for CYP3A5 and GRK4, whereas SCL4A5 was higher in the hypertensive group. The identified salt-sensitive variants specifically in GRK4 may be suggestive to be the attributing factor of the elevated BP levels in these captive-bred Vervet monkeys. Therefore, RAAS variants could be considered as a biomarker to identify the potential risk of developing hypertension in both humans and nonhuman primates.

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“…Bi-allelic variants in BOLA3 cause MMDS type 2 with hyperglycinaemia (MMDS2; MIM#614299), typically characterized by infantile encephalopathy, leukodystrophy, lactic acidosis, non-ketotic hyperglycinemia and death in early childhood [ 5 , 7 , 11 ]. Six missense and six non-sense disease-causing variants in BOLA3 have been identified to date in patients affected by MMDS2 [ 5 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Recently, a novel phenotype for MMDS2 with complete clinical recovery and partial resolution of magnetic resonance imaging abnormality was observed in a patient [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 2 Caused by CYS59TYR BOLA3 Mutation

Saudino

Suraci

Nasta

et al. 2021

IJMS

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Multiple mitochondrial dysfunctions syndrome (MMDS) is a rare neurodegenerative disorder associated with mutations in genes with a vital role in the biogenesis of mitochondrial [4Fe–4S] proteins. Mutations in one of these genes encoding for BOLA3 protein lead to MMDS type 2 (MMDS2). Recently, a novel phenotype for MMDS2 with complete clinical recovery was observed in a patient containing a novel variant (c.176G > A, p.Cys59Tyr) in compound heterozygosity. In this work, we aimed to rationalize this unique phenotype observed in MMDS2. To do so, we first investigated the structural impact of the Cys59Tyr mutation on BOLA3 by NMR, and then we analyzed how the mutation affects both the formation of a hetero-complex between BOLA3 and its protein partner GLRX5 and the iron–sulfur cluster-binding properties of the hetero-complex by various spectroscopic techniques and by experimentally driven molecular docking. We show that (1) the mutation structurally perturbed the iron–sulfur cluster-binding region of BOLA3, but without abolishing [2Fe–2S]2+ cluster-binding on the hetero-complex; (2) tyrosine 59 did not replace cysteine 59 as iron–sulfur cluster ligand; and (3) the mutation promoted the formation of an aberrant apo C59Y BOLA3–GLRX5 complex. All these aspects allowed us to rationalize the unique phenotype observed in MMDS2 caused by Cys59Tyr mutation.

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Nonketotic hyperglycinemia in captive‐bred Vervet monkeys (Chlorocebus aethiops) with cataracts

Cited by 3 publications

References 20 publications

Proprotein convertase subtilisin/kexin type 9 genetic screening using the vervet (Chlorocebus aethiops) model

Proprotein convertase subtilisin/kexin type 9 genetic screening using the vervet (Chlorocebus aethiops) model

The Association between Genetic Variants and Gene Expression in RAAS Genes Using Captive-Bred Vervet Monkeys (Chlorocebus aethiops)

Molecular Basis of Multiple Mitochondrial Dysfunctions Syndrome 2 Caused by CYS59TYR BOLA3 Mutation

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