scholarly journals Toward the Pathogenicity of the SLC26A4 p.C565Y Variant Using a Genetically Driven Mouse Model

2021 ◽  
Vol 22 (6) ◽  
pp. 2789
Author(s):  
Chin-Ju Hu ◽  
Ying-Chang Lu ◽  
Ting-Hua Yang ◽  
Yen-Hui Chan ◽  
Cheng-Yu Tsai ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Inner Ear ◽  
Cell Lines ◽  
Animal Studies ◽  
Phenotypic Characterization ◽  
Compound Heterozygous ◽  
Common Cause ◽  
The Past ◽  
Slc26a4 Gene ◽  
Ear Morphology

Recessive variants of the SLC26A4 gene are globally a common cause of hearing impairment. In the past, cell lines and transgenic mice were widely used to investigate the pathogenicity associated with SLC26A4 variants. However, discrepancies in pathogenicity between humans and cell lines or transgenic mice were documented for some SLC26A4 variants. For instance, the p.C565Y variant, which was reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice that were heterozygous (Slc26a4+/C565Y), homozygous (Slc26a4C565Y/C565Y), and compound heterozygous (Slc26a4919-2A>G/C565Y) for this variant. Subsequent phenotypic characterization revealed that mice with these genotypes demonstrated normal auditory and vestibular functions, and normal inner-ear morphology and pendrin expression. These findings indicate that the p.C565Y variant is nonpathogenic for mice, and that a single p.C565Y allele is sufficient to maintain normal inner-ear physiology in mice. Our results highlight the differences in pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be considered when interpreting the results of animal studies for SLC26A4-related deafness.

scholarly journals Toward the pathogenicity of the SLC26A4 p.C565Y variant using a genetically driven mouse model

2020 ◽  
Author(s):  
Chin-Ju Hu ◽  
Ying-Chang Lu ◽  
Ting-Hua Yang ◽  
Yen-Hui Chan ◽  
Cheng-Yu Tsai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mice ◽  
Inner Ear ◽  
Cell Lines ◽  
Animal Studies ◽  
Phenotypic Characterization ◽  
Compound Heterozygous ◽  
Common Cause ◽  
The Past ◽  
Ear Morphology

AbstractRecessive variants of the SLC26A4 gene are a common cause of hearing impairment worldwide. In the past, cell lines and transgenic mice have been widely used to investigate the pathogenicity associated with the SLC26A4 variants. However, discrepancies in the pathogenicity between humans and cell lines or transgenic mice have been documented for some of the SLC26A4 variants. For instance, the p.C565Y variant, which has been reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice heterozygous (Slc26a4+/C565Y), homozygous (Slc26a4C565Y/C565Y), and compound heterozygous (Slc26a4919-2A>G/C565Y) for this variant. Subsequent phenotypic characterization revealed that mice segregating these genotypes demonstrated normal auditory and vestibular functions and normal inner ear morphology and expression of pendrin. These findings indicate that the p.C565Y variant is non-pathogenic for mice and that a single p.C565Y allele is sufficient to maintain normal inner ear physiology in mice. Our results highlight the differences in the pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be taken into consideration while interpreting the results of animal studies for SLC26A4-related deafness.

scholarly journals Hearing from the ocean and into the river: the evolution of the inner ear of Platanistoidea (Cetacea: Odontoceti)

Paleobiology ◽  
2021 ◽  
pp. 1-21
Author(s):  
Mariana Viglino ◽  
Maximiliano Gaetán ◽  
Mónica R. Buono ◽  
R. Ewan Fordyce ◽  
Travis Park
Keyword(s):  
Inner Ear ◽  
High Frequency ◽  
Sound Production ◽  
Marine Species ◽  
Late Oligocene ◽  
Evolutionary Patterns ◽  
Ear Morphology ◽  
Cochlear Morphology ◽  
First Time ◽  
Hearing Abilities

Abstract The inner ear of the two higher clades of modern cetaceans (Neoceti) is highly adapted for hearing infrasonic (mysticetes) or ultrasonic (odontocetes) frequencies. Within odontocetes, Platanistoidea comprises a single extant riverine representative, Platanista gangetica, and a diversity of mainly extinct marine species from the late Oligocene onward. Recent studies drawing on features including the disparate tympanoperiotic have not yet provided a consensus phylogenetic hypothesis for platanistoids. Further, cochlear morphology and evolutionary patterns have never been reported. Here, we describe for the first time the inner ear morphology of late Oligocene–early Miocene extinct marine platanistoids and their evolutionary patterns. We initially hypothesized that extinct marine platanistoids lacked a specialized inner ear like P. gangetica and thus, their morphology and inferred hearing abilities were more similar to those of pelagic odontocetes. Our results reveal there is no “typical” platanistoid cochlear type, as the group displays a disparate range of cochlear anatomies, but all are consistent with high-frequency hearing. Stem odontocete Prosqualodon australis and platanistoid Otekaikea huata present a tympanal recess in their cochlea, of yet uncertain function in the hearing mechanism in cetaceans. The more basal morphology of Aondelphis talen indicates it had lower high-frequency hearing than other platanistoids. Finally, Platanista has the most derived cochlear morphology, adding to evidence that it is an outlier within the group and consistent with a >9-Myr-long separation from its sister genus Zarhachis. The evolution of a singular sound production morphology within Platanistidae may have facilitated the survival of Platanista to the present day.

scholarly journals The Past, Present and Future of Flow Cytometry in Central Nervous System Malignancies

2021 ◽  
Vol 4 (1) ◽  
pp. 11
Author(s):  
Evrysthenis Vartholomatos ◽  
George Vartholomatos ◽  
George A. Alexiou ◽  
Georgios S. Markopoulos
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Therapeutic Agents ◽  
Phenotypic Characterization ◽  
Cell Phenotype ◽  
Analytical Technique ◽  
The Past ◽  
Current Review

Central nervous system malignancies (CNSMs) are categorized among the most aggressive and deadly types of cancer. The low median survival in patients with CNSMs is partly explained by the objective difficulties of brain surgeries as well as by the acquired chemoresistance of CNSM cells. Flow Cytometry is an analytical technique with the ability to quantify cell phenotype and to categorize cell populations on the basis of their characteristics. In the current review, we summarize the Flow Cytometry methodologies that have been used to study different phenotypic aspects of CNSMs. These include DNA content analysis for the determination of malignancy status and phenotypic characterization, as well as the methodologies used during the development of novel therapeutic agents. We conclude with the historical and current utility of Flow Cytometry in the field, and we propose how we can exploit current and possible future methodologies in the battle against this dreadful type of malignancy.

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

scholarly journals Glomerular epithelial, mesangial, and endothelial cell lines from transgenic mice

1988 ◽  
Vol 33 (3) ◽  
pp. 677-684 ◽  
Author(s):  
Karen Mackay ◽  
Liliane J. Striker ◽  
Sharon Elliot ◽  
Carl A. Pinkert ◽  
Ralph L. Brinster ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Transgenic Mice ◽  
Cell Lines

scholarly journals Thyroid hormone receptor β mutations in the ‘hot-spot region’ are rare events in thyroid carcinomas

2007 ◽  
Vol 192 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Ana Sofia Rocha ◽  
Ricardo Marques ◽  
Inês Bento ◽  
Ricardo Soares ◽  
João Magalhães ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hot Spot ◽  
Direct Sequencing ◽  
Human Thyroid ◽  
Thyroid Hormone Receptor Β

Thyroid cancer constitutes the most frequent endocrine neoplasia. Targeted expression of rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) and V600E V-raf murine sarcoma viral oncogene homolog B1 (BRAF) to the thyroid glands of transgenic mice results in tumours similar to those of human PTC, providing evidence for the involvement of these oncogenes in PTC. Kato et al. developed a mouse model that mimics the full spectrum of the human follicular form of thyroid cancer (FTC). FTC rapidly develops in these mice through introduction of the thyroid hormone receptor β (THRB)PV mutant on the background of the inactivated THRB wt locus. Our aim was to verify if, in the context of human follicular thyroid carcinogenesis, THRB acted as a tumour suppressor gene. We screened for mutations of the THRB gene in the hot-spot region, spanning exons 7–10, in 51 thyroid tumours and six thyroid cancer cell lines by PCR and direct sequencing. We did not find mutations in any of the tumours or cell lines analysed. Our findings suggest that, in contrast to the findings on the THRB-mutant transgenic mice, THRB gene mutations are not a relevant mechanism for human thyroid carcinogenesis.

scholarly journals Perfluorocarbon Liquid: Its Application in Vitreoretinal Surgery and Related Ocular Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qi Yu ◽  
Kun Liu ◽  
Li Su ◽  
Xin Xia ◽  
Xun Xu
Keyword(s):  
Animal Studies ◽  
Vitreoretinal Surgery ◽  
Complete Removal ◽  
Intraocular Lenses ◽  
Perfluorocarbon Liquid ◽  
Potential Toxicity ◽  
The Past ◽  
Perfluorocarbon Liquids

The application of perfluorocarbon liquids has been well acclaimed in vitreoretinal surgery. Its unique physical properties make it an ideal intraoperative tool to improve the efficiency and safety of surgical procedures in complicated cases. The main functions of perfluorocarbon liquids in vitreoretinal surgery include relocating and fixing the detached retina, displacing the subretinal and subchoroidal to fluid anteriorly, revealing proliferative vitreous retinopathy (PVR) for further maneuvers, protecting the macula from exposure to chemicals with potential toxicity, and assisting the removal of foreign body. The related clinical applications include retinal detachment with severe proliferative vitreoretinopathy, giant tear, diabetic retinopathy (DR), retinopathy of prematurity (ROP), and posterior dislocated crystalline and intraocular lenses. The application of perfluorocarbon liquids has been expended over the past fewer years. Several PFCLs related ocular inflammations have been observed inin vitrostudies, animal studies, and clinical follow-up. The complete removal of PFCLs is recommended at the end of the surgery in most cases.

scholarly journals Calcium Signaling in Plant Programmed Cell Death

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1089
Author(s):  
Huimin Ren ◽  
Xiaohong Zhao ◽  
Wenjie Li ◽  
Jamshaid Hussain ◽  
Guoning Qi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Abiotic Stresses ◽  
Animal Studies ◽  
Future Research ◽  
Significant Progress ◽  
Biotic And Abiotic Stresses ◽  
Stress Perception ◽  
The Past

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.

Animal movement, mechanical tuning and coupled systems

1999 ◽  
Vol 202 (23) ◽  
pp. 3415-3421 ◽  
Author(s):  
T.L. Daniel ◽  
M.S. Tu
Keyword(s):  
Molecular Basis ◽  
Animal Studies ◽  
Neural Control ◽  
Animal Movement ◽  
Coupled Systems ◽  
Force Generation ◽  
Muscle Physiology ◽  
The Past ◽  
Animal Physiology ◽  
Mechanical Tuning

Over the past two decades, there has been a growing interest in developing predictive models of animal movement and force generation in fluids. In a departure from past studies that have asked how prescribed motions of a propulsor (wing or fin) generate lift and thrust during swimming and flying, we are increasingly interested in predicting the propulsor's movement as well as the forces generated by it. This interest, motivated by a need to understand the control and dynamics of locomotion and its applications to robotics and animal physiology, requires that we develop integrative models and analyses of swimming and flying that incorporate neural control and muscle physiology into more traditional biomechanical studies of locomotion in fluids. This approach extends from whole-animal studies to the molecular basis of force generation. In this paper, we explore mechanical tuning from the level of the whole animal to the proteins driving force generation in muscle.

Asthma and Pneumomediastinum

PEDIATRICS ◽  
1985 ◽  
Vol 75 (5) ◽  
pp. 990-990
Author(s):  
ROBERT G. ZWERDLING
Keyword(s):  
Case Report ◽  
Childhood Asthma ◽  
Mediastinal Emphysema ◽  
Review Of The Literature ◽  
Common Cause ◽  
The Past ◽  
Treatable Condition

To the Editor.— Sturtz's case report and brief review of the literature on spontaneous mediastinal emphysema is interesting.1 However, he neglects to mention what is perhaps the most common cause of this condition in childhood—asthma. Indeed, reports of this complication have occurred over the past 130 years.2-4 Recognition of this fact often results in an understanding of the cause for the pneumomediastinum as well as tipping the clinician off to a possibly undiagnosed but readily treatable condition.

Sign in / Sign up

Export Citation Format

Share Document