YIPF5 (p.W218R) mutation induced primary microcephaly in rabbits

Liu, Xin; Yang, Jie; Li, Zhaoyi; Liu, Ruonan; Wu, Xinyu; Zhang, Zhongtian; Lai, Liangxue; Li, Zhanjun; Song, Yuning

doi:10.1016/j.nbd.2023.106135

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…A homozygous missense mutation in YIPF5 was previously identified as a causative mutation of severe microcephaly. Using the adenine base editor SpRY-ABEmax, a genome-edited rabbit model harboring the YIPF5 (p. W218R) mutation was established in 2023 ( Liu et al, 2023 ), better mimicking the clinical features of human primary microcephaly compared to mice. Subsequent research using these rabbit models has revealed that alterations in YIPF5 function may lead to endoplasmic reticulum stress and neurological developmental disorders.…”

Section: Generation Of Genome-edited Rabbits In Biomedical Researchmentioning

confidence: 99%

“…Subsequent research using these rabbit models has revealed that alterations in YIPF5 function may lead to endoplasmic reticulum stress and neurological developmental disorders. The link between endoplasmic reticulum stress-induced unfolded protein response (UPR) and the development of primary microcephaly with or without pontocerebellar hypoplasia (PMCPH) has also been established, shedding light on the role of YIPF5 in human brain development and providing a theoretical basis for the differential diagnosis and clinical treatment of PMCPH ( Liu et al, 2023 ). Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects spinal cord and cortical motor neurons.…”

Section: Generation Of Genome-edited Rabbits In Biomedical Researchmentioning

confidence: 99%

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Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases

Han,

Zhou,

Zhang

et al. 2024

Zoological Research

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Animal models are extensively used in all aspects of biomedical research, with substantial contributions to our understanding of diseases, the development of pharmaceuticals, and the exploration of gene functions. The field of genome modification in rabbits has progressed slowly. However, recent advancements, particularly in CRISPR/Cas9-related technologies, have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases, including cardiovascular disorders, immunodeficiencies, aging-related ailments, neurological diseases, and ophthalmic pathologies. These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice. This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine, underscoring their impact and future potential in translational medicine.

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Section: Generation Of Genome-edited Rabbits In Biomedical Researchmentioning

confidence: 99%

Section: Generation Of Genome-edited Rabbits In Biomedical Researchmentioning

confidence: 99%

Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases

Han,

Zhou,

Zhang

et al. 2024

Zoological Research

View full text Add to dashboard Cite

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“…Cytokinesis failure, characteristic of some microcephaly models ( Di Cunto et al, 2000 ; Higgins et al, 2010 ; Harding et al, 2016 ; Perez et al, 2019 ; Reilly et al, 2019 ; Tedeschi et al, 2020 ; Little et al, 2021 ) has been reported to stabilize TP53 by engaging the Hippo pathway ( Ganem et al, 2014 ). The unfolded protein response (UPR), which has been documented in specific genetic microcephaly syndromes ( Laguesse et al, 2015 ; Passemard et al, 2019 ; Terabayashi and Hashimoto, 2021 ; Liu et al, 2023 ), and could be generally engaged by aneuploidy ( Zanetti et al, 2016 ), may activate TP53 through NFkB engagement ( Lin et al, 2012 ). Finally, disruption of centrosomal function, which may be produced by many MCPH mutations ( Robinson et al, 2020 ), may stimulate P53 activity through the 53BP1-USP28 axis ( Cuella-Martin et al, 2016 ; Meitinger et al, 2016 ).…”

Section: Mechanisms Of Tp53 Activation In Mcph: Dna Damage and Beyondmentioning

confidence: 99%

The impact of TP53 activation and apoptosis in primary hereditary microcephaly

et al. 2023

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Autosomal recessive primary microcephaly (MCPH) is a constellation of disorders that share significant brain size reduction and mild to moderate intellectual disability, which may be accompanied by a large variety of more invalidating clinical signs. Extensive neural progenitor cells (NPC) proliferation and differentiation are essential to determine brain final size. Accordingly, the 30 MCPH loci mapped so far (MCPH1-MCPH30) encode for proteins involved in microtubule and spindle organization, centriole biogenesis, nuclear envelope, DNA replication and repair, underscoring that a wide variety of cellular processes is required for sustaining NPC expansion during development. Current models propose that altered balance between symmetric and asymmetric division, as well as premature differentiation, are the main mechanisms leading to MCPH. Although studies of cellular alterations in microcephaly models have constantly shown the co-existence of high DNA damage and apoptosis levels, these mechanisms are less considered as primary factors. In this review we highlight how the molecular and cellular events produced by mutation of the majority of MCPH genes may converge on apoptotic death of NPCs and neurons, via TP53 activation. We propose that these mechanisms should be more carefully considered in the alterations of the sophisticated equilibrium between proliferation, differentiation and death produced by MCPH gene mutations. In consideration of the potential druggability of cell apoptotic pathways, a better understanding of their role in MCPH may significantly facilitate the development of translational approaches.

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“…In previous studies, CRISPR/Cas9 technique was applied to introduce mutation of αA-Crystallin or GJA8 gene to induce congenital cataracts in Rabbits ( Yuan et al, 2016 ; Yuan et al, 2017 ). Recently, SpRY-ABEmax mediated base substitution has been used to generate YIPF5 (p.W218R) mutation to generate rabbit primary microcephaly model, which precisely recapitulate the typical symptoms of human primary microcephaly ( Liu et al, 2023 ). With recent technological innovations in genomic editing techniques, rabbit models will certainly play a much more important role in the study on human diseases.…”

Section: Rabbitmentioning

confidence: 99%