Related Experiment Video
Updated: Jul 16, 2025
08:17
Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo
Published on: September 22, 2017
19.3K
Genetic background modulates phenotypic expressivity in OPA1 mutated mice, relevance to DOA pathogenesis
Djamaa Atamena1, Venu Gurram1, Petnoï Petsophonsakul1
1Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Toulouse III, CNRS, Toulouse, France.
Frontiers in Molecular Neuroscience
|September 22, 2023
Summary
Dominant optic atrophy (DOA) variability is influenced by genetic background. Modifying genes impact disease severity, suggesting new diagnostic and therapeutic strategies for this optic nerve degeneration.
Area of Science:
- Genetics
- Neuroscience
- Ophthalmology
Background:
- Dominant optic atrophy (DOA) is an inherited optic neuropathy caused by OPA1 mutations.
- DOA exhibits incomplete penetrance and highly variable expressivity, suggesting modifying factors influence disease severity.
- Current understanding lacks a clear genotype-phenotype correlation in DOA.
Purpose of the Study:
- To investigate the influence of genetic background on DOA expressivity.
- To analyze the impact of a pure C57BL/6J background on a previously established DOA mouse model.
- To explore potential early diagnostic markers and therapeutic targets for DOA.
Main Methods:
- A mouse model of DOA with an Opa1 mutation was switched from a mixed C3H;C57BL/6J background to a pure C57BL/6J background.
- Retinal and optic nerve abnormalities were assessed.
- Retinal ganglion cell (RGC) connectivity and potential degeneration were evaluated.
Main Results:
- Absence of retinal and optic nerve degeneration was observed in the pure C57BL/6J background.
- A sex-dependent negative effect on RGC connectivity was identified.
- Evidence suggests RGC synaptic alterations may precede neuronal death in DOA.
Conclusions:
- Genetic background significantly modulates DOA expressivity.
- RGC synaptic alterations could serve as an early indicator for DOA, opening therapeutic windows.
- This study provides a model for identifying environmental and genetic factors influencing DOA progression.
Related Concept Videos
01:11Genetic Lingo
103.0K
Overview
103.0K
01:33Pleiotropy
40.6K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
40.6K
01:09Epistasis Analysis
5.0K
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
5.0K
01:28Human Genetics
601
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
601
02:27Background and Environment Affect Phenotype
6.6K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
6.6K
02:41Lethal Alleles
15.5K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.5K