Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis

Human Genetics
Tang HaiJianguo Zhao

Abstract

Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF+/L247S) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITFL247S/L247S) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better underst...Continue Reading

References

Nov 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·W L RussellE L Phipps
Feb 1, 1990·The Journal of Laryngology and Otology·V Newton
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·B B Riley, D J Grunwald
Jan 2, 1995·American Journal of Medical Genetics·X Z LiuA P Read
Nov 1, 1995·Human Molecular Genetics·M TassabehjiW Reardon
Aug 1, 1997·Journal of Medical Genetics·A P Read, V E Newton
Jun 14, 2000·Journal of Medical Genetics·S D SmithD Hoover
Aug 10, 2000·Nature Genetics·M H Hrabé de AngelisR Balling
Jun 24, 2003·The American Journal of Pathology·Jinyan DuDavid E Fisher
Sep 3, 2003·Pigment Cell Research·Masayoshi TachibanaYoshibumi Matsushima
Nov 14, 2003·Genome Research·Erno WienholdsEdwin Cuppen
Dec 4, 2003·Gene Expression Patterns : GEP·Laura L Baxter, William J Pavan
Dec 1, 2004·Annual Review of Genetics·Eiríkur SteingrímssonNancy A Jenkins
Jan 11, 2007·BMC Genomics·Robert GeislerChristiane Nüsslein-Volhard
Feb 3, 2007·Biochemical and Biophysical Research Communications·Fatima LekmineGeorge I Salti
Aug 2, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Amit KochharRichard J H Smith
Nov 30, 2007·Journal of Microscopy·J M Lovell, G M Harper
Oct 25, 2008·Annual Review of Genomics and Human Genetics·Abraham Acevedo-ArozenaSteve D M Brown
Feb 12, 2009·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·S StritzelO Distl
Jul 15, 2009·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·André GurrS Dazert
Oct 1, 1992·Molecular and Cellular Neurosciences·M TachibanaH Arnheiter
Dec 17, 2009·Breast Cancer Research : BCR·Ana-Teresa MaiaBruce A J Ponder
May 19, 2010·Biochemical and Biophysical Research Communications·Hongsheng ChenYong Feng
Jan 4, 2012·Annals of the New York Academy of Sciences·Eric M WaltersTim Evans
Aug 16, 2012·Human Molecular Genetics·Peter L Oliver, Kay E Davies
Nov 15, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Weiwei GuoShi-Ming Yang
Jun 24, 2015·Clinical Genetics·J SongI J Dhooge

❮ Previous
Next ❯

Citations

Jan 9, 2019·Marine Biotechnology·Wanwan ZhangMeisheng Yi
Feb 20, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Feng-Wei AnShi-Ming Yang
Mar 30, 2019·Journal of Molecular Cell Biology·Xiao WangJianguo Zhao
Aug 18, 2020·Neural Plasticity·Linjun ChenShiming Yang
Sep 6, 2019·Acta Oto-laryngologica·Xiao-Jun JiShi-Ming Yang
Jul 17, 2018·BioMed Research International·Min Yong Lee, Yong-Ho Park
Nov 18, 2018·EMBO Molecular Medicine·Hongyong ZhangQi Zhou
Aug 28, 2019·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Jun YaoYifan Dai
Feb 20, 2021·Frontiers in Genetics·Iuri Viotti PerisseIrina A Polejaeva
Feb 23, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xiaoxue LiYifan Dai
Jun 22, 2020·Journal of Equine Veterinary Science·Sergio Navarro-SernaPablo Juan Ross
Apr 27, 2020·Hearing Research·Philipp NiggemannZheng-Yi Chen
Apr 13, 2021·The Journal of Reproduction and Development·Fuminori TaniharaTakeshige Otoi
Jun 20, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Jinfu ZhangShengsong Xie
Jul 30, 2021·Molecular Genetics & Genomic Medicine·Jing WangHuijun Yuan

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
PCR
light microscopy
in vitro transcription
electrophoresis
transfections
Assay
scanning electron microscopy
cochlear section

Software Mentioned

PLINK
Merlin

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Related Papers

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
Antonella Castaldo, Fred H Linthicum
Journal of Neurophysiology
I TASAKI, C S SPYROPOULOS
© 2022 Meta ULC. All rights reserved