The DBA mouse is a widely used laboratory animal model in scientific research, offering unique insights into human biology and disease. Its consistent genetic makeup allows for reliable and reproducible studies, making it a foundational tool for understanding how genetic factors influence health and disease.
Defining the DBA Mouse
The DBA mouse is an inbred strain of laboratory mouse, bred through many generations of brother-sister matings to achieve genetic uniformity. This process ensures nearly all individuals within the strain are genetically identical, with at least 98.6% of their loci being homozygous after 20 generations of inbreeding. This genetic consistency is invaluable for research, as it minimizes variability between subjects, allowing scientists to attribute observed outcomes directly to experimental interventions. The DBA strain was the first inbred mouse strain ever developed, established in 1909 by Clarence Cook Little at the Bussey Institute for Research in Applied Biology at Harvard University.
The name “DBA” is an acronym reflecting its distinctive coat color: “Dilute Brown, Non-Agouti.” The strain originated from mice carrying three recessive genes—dilution (d), brown (b), and non-agouti (a)—which collectively determine this specific coloration. Over time, the original DBA strain diverged into several substrains, with DBA/1 and DBA/2 being the most prominent. These substrains, established around 1929-1930, exhibit differences in various genetic loci, including their Major Histocompatibility Complex (MHC) haplotype, which impacts their immune responses.
Distinctive Biological Traits
DBA mice possess several well-characterized biological and genetic traits that make them valuable for specific areas of research. A notable characteristic, especially in the DBA/2J substrain, is progressive hearing loss. This impairment begins early, affecting high frequencies around 3-4 weeks of age and becoming severe by 2-3 months. The hearing loss is linked to a mutation in the Cdh23 gene (Cdh23ahl), which leads to age-related hearing loss and progressive cochlear pathology.
Another distinctive trait is their susceptibility to audiogenic seizures, induced by loud sounds. Young DBA/2J mice are prone to these seizures due to the asp2 mutation, though this susceptibility generally decreases as the animals reach adulthood.
The DBA/2J substrain is also predisposed to certain eye conditions that mimic human hereditary glaucoma. Symptoms of eye health decline, including the loss of retinal ganglion cells and amacrine cells, can begin at a few months of age and tend to be more severe in females. Glaucoma in DBA/2J mice is associated with iris stromal atrophy and pigment dispersion, which can lead to increased intraocular pressure.
Key Contributions to Scientific Research
The distinctive biological traits of DBA mice have led to contributions across various scientific and medical research fields. Their progressive hearing loss makes them a widely used model for studying hearing impairment and developing potential therapies. Researchers use DBA/2J mice to investigate auditory degeneration and explore genetic factors involved in age-related hearing loss.
DBA mice, particularly the DBA/2 substrain, serve as a model for epilepsy and other neurological disorders due to their susceptibility to audiogenic seizures. These sound-induced seizures mimic aspects of human epilepsy and sudden unexpected death in epilepsy (SUDEP). This model allows researchers to investigate seizure disorder mechanisms and evaluate new anticonvulsant drugs and potential treatments for SUDEP.
The DBA/2J mouse is used in glaucoma research because it spontaneously develops a form of glaucoma resembling human open-angle glaucoma. This model allows scientists to study disease progression, including increased intraocular pressure and loss of retinal ganglion cells. Research using DBA/2J mice has helped identify molecular changes associated with glaucoma development, aiding the search for new diagnostic biomarkers and therapeutic interventions.
DBA mice also contribute to immunology research due to their unique immunological profiles. For example, DBA/1 mice are commonly used to model rheumatoid arthritis, developing severe joint inflammation when exposed to type II collagen. This makes them suitable for testing anti-inflammatory drugs and studying autoimmune mechanisms. Their specific immune responses also make them valuable for studying other autoimmune diseases and general immune system function. Beyond specific disease models, DBA mice are widely employed in pharmacology and drug development to test the efficacy and safety of new drugs for conditions related to their characteristic traits.