Related Experiment Video
Updated: Aug 5, 2026
Gene Editing of Primary Rhesus Macaque B Cells
Published on: February 10, 2023
A WHRN mutation impacts ocular morphology in rhesus macaques
Ana Ripolles-Garcia1, Ana Raposo1, Sophie M Le1
1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, United States.
Background:
Rhesus macaques are increasingly used to model inherited sensory disorders, yet the phenotypic impact of naturally occurring variants in primate colonies often remains undefined.
Methods:
We identified five rhesus macaques homozygous for a missense variant in WHRN (p.Val495Met in exon 7), which encodes whirlin and is implicated in human Usher syndrome type 2D, and compared them with five age and sex matched wild-type controls (WHRN homozygotes: mean age 9.4 ± 1.8 years; controls: mean age 8.6 ± 1.1 years) using standardized ocular and auditory phenotyping, including comprehensive ophthalmic examination, A-scan ocular biometry, intraocular pressure measurement, cycloplegic refraction, macular optical coherence tomography with retinal layer thickness quantification, full-field electroretinography, and brainstem auditory evoked response testing.
Results:
WHRN homozygotes showed a consistent shift in ocular component dimensions, with significantly reduced lens thickness, while refractive error remained centered near emmetropia. By contrast, fundus examination and macular optical coherence tomography showed preserved retinal morphology, electroretinography waveforms were comparable between groups, and brainstem auditory evoked responses did not show evidence of overt hearing impairment under the recording conditions used.
Conclusion:
These findings define a subtle ocular biometry phenotype associated with WHRN p. Val495Met homozygosity in rhesus macaques, while retinal structure and function were preserved at the time of testing; more comprehensive auditory phenotyping across frequencies and thresholds will be needed to assess whether subtle, frequency specific hearing deficits consistent with an atypical Usher presentation are present.
Insights
Rhesus macaques with a whirlin (WHRN) gene variant show altered eye measurements but preserved retinal structure. Further auditory testing is needed to rule out subtle hearing deficits.
Area of Science:
- Genetics
- Ophthalmology
- Audiology
Background:
- Rhesus macaques are valuable models for inherited sensory disorders.
- Naturally occurring genetic variants in primate models often lack defined phenotypic impact.
- Understanding these variants is crucial for accurate disease modeling.
Purpose of the Study:
- To investigate the phenotypic consequences of a specific WHRN gene variant in rhesus macaques.
- To compare ocular and auditory function in macaques homozygous for WHRN p.Val495Met with wild-type controls.
- To assess the utility of these macaques as models for Usher syndrome.
Main Methods:
- Identified five rhesus macaques homozygous for the WHRN p.Val495Met variant.
- Compared them with five age- and sex-matched wild-type controls.
- Conducted comprehensive ocular and auditory phenotyping, including biometry, imaging, electroretinography, and brainstem auditory evoked response testing.
Main Results:
- WHRN homozygotes exhibited significantly reduced lens thickness but maintained emmetropic refractive error.
- Retinal morphology and electroretinography waveforms were comparable between groups.
- Brainstem auditory evoked responses showed no overt hearing impairment under tested conditions.
Conclusions:
- Homozygosity for WHRN p.Val495Met results in a subtle ocular biometry phenotype in rhesus macaques.
- Retinal structure and function appear preserved at the time of testing.
- Further auditory phenotyping is required to detect potential subtle, frequency-specific hearing deficits characteristic of atypical Usher syndrome.
