An L1 retrotransposon insertion–induced deafness mouse model for studying the development and function of the cochlear stria vascularis

Dysregulation of ion and potential homeostasis in the scala media is the most prevalent cause of hearing loss in mammals. However, it is not well understood how the development and function of the stria vascularis regulates this fluid homeostasis in the scala media. From a mouse genetic screen, we characterize a mouse line, named 299, that displays profound hearing impairment. Histology suggests that 299 mutant mice carry a severe, congenital structural defect of the stria vascularis. The in vivo recording of 299 mice using double-barreled electrodes shows that endocochlear potential is abolished and potassium concentration is reduced to ∼20 mM in the scala media, a stark contrast to the +80 mV endocochlear potential and the 150 mM potassium concentration present in healthy control mice. Genomic analysis revealed a roughly 7-kb-long, interspersed nuclear element (LINE-1 or L1) retrotransposon insertion on chromosome 11. Strikingly, the deletion of this L1 retrotransposon insertion from chromosome 11 restored the hearing of 299 mutant mice. In summary, we characterize a mouse model that enables the study of stria vascularis development and fluid homeostasis in the scala media.

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Transcript profiles of stria vascularis in models of Waardenburg syndrome

10.21203/rs.2.16137/v1 ◽

2019 ◽

Author(s):

Linjun Chen ◽

Yi Wang ◽

Lei Chen ◽

Fangyuan wang ◽

Fei Ji ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Mouse Models ◽

Stria Vascularis ◽

Specific Gene ◽

Waardenburg Syndrome ◽

Significant Difference ◽

Tyrosine Metabolism ◽

Transcript Profiles ◽

And Function

Abstract Background: Waardenburg syndrome is a common syndromic hereditary deafness disease caused by stria vascularis dysfunction. However, the genetic pathway affecting stria vascularis development is still not clear. In this paper, the transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pigs and mice models. GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results: There were over than one hundred genes mainly found in tyrosine metabolism, melanin formation and ion transportations showed significant changes in both models. In addition, there were some spiced specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19 and Cdh24 genes , were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1 and Col11a2 genes were higher and the expression of Col8a2, Cd34 and Ncam genes were lower in the porcine model compared to mouse model. In both models, Trpm1, Kcnj13, and Slc45a2 genes were both affected by the Mitf-M mutation. In the pig models, the expression of Kcnn1, Clcn2 and Trpm4 genes were higher than the mouse model; whereas the expression of Trpm7, Kcnq1 and Kcnj8 genes were higher in the mouse models than the pig models. However, there was no significant difference in the morphology of the stria vascularis between these two models. Conclusions: Our data suggests that there is a significant difference on the gene expression and function between these two models.

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Transcript profiles of stria vascularis in models of Waardenburg syndrome

10.21203/rs.2.14502/v1 ◽

2019 ◽

Author(s):

Linjun Chen ◽

Yi Wang ◽

Lei Chen ◽

Fangyuan Wang ◽

Fe Ji ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Mouse Models ◽

Stria Vascularis ◽

Specific Gene ◽

Waardenburg Syndrome ◽

Significant Difference ◽

Tyrosine Metabolism ◽

Transcript Profiles ◽

And Function

Abstract Background: Waardenburg syndrome is a common syndromic hereditary deafness disease caused by stria vascularis dysfunction. However, the genetic pathway affecting stria vascularis development is still not clear. In this paper, the transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pigs and mice models. GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results: There were over than one hundred genes mainly found in tyrosine metabolism, melanin formation and ion transportations showed significant changes in both models. In addition, there were some spiced specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19 and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1 and Col11a2 genes were higher and the expression of Col8a2, Cd34 and Ncam genes were lower in the porcine model compared to mouse model. In both models, Trpm1, Kcnj13, and Slc45a2 genes were both affected by the Mitf-M mutation. In the pig models, the expression of Kcnn1, Clcn2 and Trpm4 genes were higher than the mouse model; whereas the expression of Trpm7, Kcnq1 and Kcnj8 genes were higher in the mouse models than the pig models. However, there was no significant difference in the morphology of the stria vascularis between these two models. Conclusions: Our data suggests that there is a significant difference on the gene expression and function between these two models.

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Faculty Opinions recommendation of Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5579962.6144054 ◽

2010 ◽

Author(s):

Roger Barker ◽

Wei-Li Kuan

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Motor Neuron ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

And Function ◽

Lateral Sclerosis

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Faculty Opinions recommendation of Development and function of human innate immune cells in a humanized mouse model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718312148.793492680 ◽

2014 ◽

Author(s):

Gerald Spangrude

Keyword(s):

Mouse Model ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

And Function

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Breeder Diet Strategies for Generating Ttpa-Null and Wild-Type Mice with Low Vitamin E Status to Assess Neurological Outcomes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa155 ◽

2020 ◽

Vol 4 (11) ◽

Author(s):

Katherine M Ranard ◽

Matthew J Kuchan ◽

John W Erdman

Keyword(s):

Animal Model ◽

Vitamin E ◽

Mouse Model ◽

Wild Type ◽

Future Studies ◽

Neurological Outcomes ◽

Transfer Protein ◽

And Function ◽

The Brain ◽

Vitamin E Status

ABSTRACT Studying vitamin E [α-tocopherol (α-T)] metabolism and function in the brain and other tissues requires an animal model with low α-T status, such as the transgenic α-T transfer protein (Ttpa)–null (Ttpa−/−) mouse model. Ttpa+/− dams can be used to produce Ttpa−/− and Ttpa+/+mice for these studies. However, the α-T content in Ttpa+/− dams’ diet requires optimization; diets must provide sufficient α-T for reproduction, while minimizing the transfer of α-T to the offspring destined for future studies that require low baseline α-T status. The goal of this work was to assess the effectiveness and feasibility of 2 breeding diet strategies on reproduction outcomes and offspring brain α-T concentrations. These findings will help standardize the breeding methodology used to generate the Ttpa−/− mice for neurological studies.

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