Knock-In Mice with Myo3a Y137C Mutation Displayed Progressive Hearing Loss and Hair Cell Degeneration in the Inner Ear

Li, Peipei; Wen, Zongzhuang; Zhang, Guangkai; Zhang, Aizhen; Fu, Xiaolong; Gao, Jiangang

doi:10.1155/2018/4372913

Cited by 16 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used CRISPR-Cas9 genome-editing technology to obtain the Piccolo knockout mouse model in the CBA/CaJ mouse line. The CRISPR-Cas9 genome-editing technology was used as previously described [ 58 , 59 ]. The pX330 plasmid was obtained from Addgene (Plasmid ID: #42230).…”

Section: Methodsmentioning

confidence: 99%

Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function

Lin

et al. 2021

Aging

Self Cite

View full text Add to dashboard Cite

Piccolo is a presynaptic protein with high conservation among different species, and the expression of Piccolo is extensive in vertebrates. Recently, a small fragment of Piccolo (Piccolino), arising due to the incomplete splicing of intron 5/6, was found to be present in the synapses of retinas and cochleae. However, the comprehensive function of Piccolo in the retina and cochlea remains unclear. In this study, we generated Piccolo knockout mice using CRISPR-Cas9 technology to explore the function of Piccolo. Unexpectedly, whereas no abnormalities were found in the cochlear hair cells of the mutant mice, significant differences were found in the retinas, in which two layers (the outer nuclear layer and the outer plexiform layer) were absent. Additionally, the amplitudes of electroretinograms were significantly reduced and pigmentation was observed in the fundoscopy of the mutant mouse retinas. The expression levels of Bassoon, a homolog of Piccolo, as well as synapse-associated proteins CtBP1, CtBP2, Kif3A, and Rim1 were down-regulated. The numbers of ribbon synapses in the retinas of the mutant mice were also reduced. Altogether, the phenotype of Piccolo -/- mice resembled the symptoms of retinitis pigmentosa (RP) in humans, suggesting Piccolo might be a candidate gene of RP and indicates Piccolo knockout mice are a good model for elucidating the molecular mechanisms of RP.

show abstract

Section: Methodsmentioning

confidence: 99%

Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function

Lin

et al. 2021

Aging

Self Cite

View full text Add to dashboard Cite

show abstract

“…We identified very rare PLP ARNSHI variants in three known genes ( MYO3A , MYO15A and COL9A3 ) ( Table 2 ). MYO3A was first associated with progressive ARNSHI in a multigenerational Israeli family ( 31 ) and has since been associated with progressive HI in mice ( 32 ). A recessive form of HI with pathologic variants in MYO3A has also been reported in a Chinese family ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing reveals pathogenic variants inMYO3A,MYO15AandCOL9A3and differential frequencies in ancestral alleles in hearing impairment genes among individuals from Cameroon

Wonkam

Manyisa

Bope

et al. 2020

Human Molecular Genetics

View full text Add to dashboard Cite

There is scarcity of known gene variants of Hearing Impairment (HI) in African populations. This knowledge deficit is ultimately affecting the development of genetic diagnoses. We used whole exome sequencing to investigate gene variants, pathways of interactive genes, and the fractions of ancestral over derived alleles for 159 HI genes, among 18 Cameroonian patients with non-syndromic HI (NSHI), and 129 ethnically matched controls. Pathogenic and likely pathogenic (PLP) variants were found in MYO3A, MYO15A and COL9A3, with a resolution rate of 50% (9/18 patients). The study identified significant genetic differentiation in novel population specific gene variants at FOXD4L2, DHRS2L6, RPL3L and VTN, between HI patients and controls. These gene variants are found in functional/co-expressed interactive networks with other known HI associated genes; and in the same pathways with VTN being a hub protein, i.e. focal adhesion pathway and regulation of the actin cytoskeleton (p values < 0.05). The results suggest that these novel population specific gene variants are possible modifiers of the HI phenotypes. We found a high proportion of ancestral allele vs derived at low HI patients-specific minor allele frequency in range of 0.0 to 0.1. The results showed a relatively low pick up rate of PLP variants in known genes in this group of Cameroonian patients with NSHI. In addition, findings may signal an evolutionary enrichment of some variants of HI genes in patients, as the result of polygenic adaptation, and suggest the possibility of multigenic influence on the phenotype of congenital HI, which deserves further investigations.

show abstract

“…Among numerous model animals, mice are widely used for scientific studies and recognized as the most important model animals in human disease research [83] . So far, researchers have successfully generated many genetically modified mouse models, such as cancer, cardiovascular disease, cardiomyopathy, Huntington's disease, albino, deafness, hemophilia B, obesity, urea cycle disorder and muscular dystrophy [84] , [85] , [86] , [87] , [88] , [89] , [90] , [91] , [92] , [93] . Nevertheless, owing to the great species differences between humans and rodents, they can’t provide effective assessment and long-term follow-up for research and treatment of human diseases [94] .…”

Section: Applications Of Crispr-cas Systems In Human Disease Researchmentioning

confidence: 99%

CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

2020

Computational and Structural Biotechnology Journal

182

View full text Add to dashboard Cite

Genome editing is the modification of genomic DNA at a specific target site in a wide variety of cell types and organisms, including insertion, deletion and replacement of DNA, resulting in inactivation of target genes, acquisition of novel genetic traits and correction of pathogenic gene mutations. Due to the advantages of simple design, low cost, high efficiency, good repeatability and short-cycle, CRISPR-Cas systems have become the most widely used genome editing technology in molecular biology laboratories all around the world. In this review, an overview of the CRISPR-Cas systems will be introduced, including the innovations, the applications in human disease research and gene therapy, as well as the challenges and opportunities that will be faced in the practical application of CRISPR-Cas systems.

show abstract

Knock-In Mice with Myo3a Y137C Mutation Displayed Progressive Hearing Loss and Hair Cell Degeneration in the Inner Ear

Cited by 16 publications

References 41 publications

Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function

Piccolo is essential for the maintenance of mouse retina but not cochlear hair cell function

Whole exome sequencing reveals pathogenic variants inMYO3A,MYO15AandCOL9A3and differential frequencies in ancestral alleles in hearing impairment genes among individuals from Cameroon

CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

Contact Info

Product

Resources

About