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.



Disease Annotations    
Deafness  (IAGP,ISO)
Usher Syndrome Type 1B  (IAGP,ISO)

Phenotype Annotations    

Mammalian Phenotype
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