RGD Reference Report - Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics. - Rat Genome Database

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Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics.

Authors: Smits, BM  Peters, TA  Mul, JD  Croes, HJ  Fransen, JA  Beynon, AJ  Guryev, V  Plasterk, RH  Cuppen, E 
Citation: Smits BM, etal., Genetics. 2005 Aug;170(4):1887-96. Epub 2005 Jun 18.
RGD ID: 1581470
Pubmed: PMID:15965244   (View Abstract at PubMed)
PMCID: PMC1449770   (View Article at PubMed Central)
DOI: DOI:10.1534/genetics.105.044222   (Journal Full-text)

The rat is the most extensively studied model organism and is broadly used in biomedical research. Current rat disease models are selected from existing strains and their number is thereby limited by the degree of naturally occurring variation or spontaneous mutations. We have used ENU mutagenesis to increase genetic variation in laboratory rats and identified a recessive mutant, named tornado, showing aberrant circling behavior, hyperactivity, and stereotypic head shaking. More detailed analysis revealed profound deafness due to disorganization and degeneration of the organ of Corti that already manifests at the onset of hearing. We set up a single nucleotide polymorphism (SNP)-based mapping strategy to identify the affected gene, revealing strong linkage to the central region of chromosome 1. Candidate gene resequencing identified a point mutation that introduces a premature stopcodon in Myo7a. Mutations in human MYO7A result in Usher syndrome type 1B, a severe autosomal inherited recessive disease that involves deafness and vestibular dysfunction. Here, we present the first characterized rat model for this disease. In addition, we demonstrate proof of principle for the generation and cloning of human disease models in rat using ENU mutagenesis, providing good perspectives for systematic phenotypic screens in the rat.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MYO7AHumanDeafness  ISOMyo7a (Rattus norvegicus)DNA:nonsense mutation:cdsRGD 
Myo7aRatDeafness  IAGP DNA:nonsense mutation:cdsRGD 
Myo7aMouseDeafness  ISOMyo7a (Rattus norvegicus)DNA:nonsense mutation:cdsRGD 
MYO7AHumanUsher Syndrome Type 1B  ISOMyo7a (Rattus norvegicus)DNA:nonsense mutationRGD 
Myo7aRatUsher Syndrome Type 1B  IAGP DNA:nonsense mutationRGD 
Myo7aMouseUsher Syndrome Type 1B  ISOMyo7a (Rattus norvegicus)DNA:nonsense mutationRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Myo7aRatabnormal auditory brainstem response  IAGP DNA:nonsense mutation:cdsRGD 
Myo7atnd/HubrRatabnormal auditory brainstem response  IAGP DNA:nonsense mutation:cdsRGD 
W-Myo7atnd/HubrRatabnormal auditory brainstem response  IAGP DNA:nonsense mutation:cdsRGD 
Myo7aRatabnormal cochlear hair cell stereociliary bundle morphology  IAGP DNA:nonsense mutation:cdsRGD 
Myo7atnd/HubrRatabnormal cochlear hair cell stereociliary bundle morphology  IAGP DNA:nonsense mutation:cdsRGD 
W-Myo7atnd/HubrRatabnormal cochlear hair cell stereociliary bundle morphology  IAGP DNA:nonsense mutation:cdsRGD 
Myo7aRatabnormal vestibular system physiology  IAGP DNA:nonsense mutation:cdsRGD 
Myo7atnd/HubrRatabnormal vestibular system physiology  IAGP DNA:nonsense mutation:cdsRGD 
W-Myo7atnd/HubrRatabnormal vestibular system physiology  IAGP DNA:nonsense mutation:cdsRGD 
Myo7aRatcircling  IAGP DNA:nonsense mutation:cdsRGD 
Myo7atnd/HubrRatcircling  IAGP DNA:nonsense mutation:cdsRGD 
W-Myo7atnd/HubrRatcircling  IAGP DNA:nonsense mutation:cdsRGD 
Myo7aRathyperactivity  IAGP DNA:nonsense mutation:cdsRGD 
Myo7atnd/HubrRathyperactivity  IAGP DNA:nonsense mutation:cdsRGD 
W-Myo7atnd/HubrRathyperactivity  IAGP DNA:nonsense mutation:cdsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Myo7a  (myosin VIIA)
Myo7atnd/Hubr  (myosin VIIA; ENU induced tornado mutant, Hubr)

Genes (Mus musculus)
Myo7a  (myosin VIIA)

Genes (Homo sapiens)
MYO7A  (myosin VIIA)

Strains
W-Myo7atnd/Hubr  (Wistar tornado rat)


Additional Information