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Zhang et al. Ageing Neur Dis 2022;2:16 https://dx.doi.org/10.20517/and.2022.15 Page 7 of 11

[88,89]
CRISPR/Cas9 ROSA 26 KI Safe harbor gene
[90]
BE3 MSTN p.Q93stop Muscle hypertrophy
TYR p.Q68stop Oculocutaneous albinism
ABE7.10 DMD p.T279A Duchenne muscular dystrophy
[91]
eAID- TYR p.R299H Oculocutaneous albinism
BE4max
[92]
YFE-BE4max TYR p.Q68Stop Oculocutaneous albinism
[93]
nNme2-CBE FGF5 p.Q79Stop Long hair
[94]
eA3G-BE TYR p.Q48stop Oculocutaneous albinism
[95]
NG-ABEmax HOXC13 p.Q271R Hair and nail ectodermal dysplasia
[96]
BE4max FGF5 Start Codon Long hair
Disruption
ABE8.17 TYR p.T325A Oculocutaneous albinism [97]
LMNA p.L530P Emery-Dreifuss muscular dystrophy
PE3 HEXA p.Y427fs Tay-Sachs disease [98]

PROSPECTS AND LIMITATIONS FOR EVALUATING RABBIT DISEASE MODELS
The observation of the clinical phenotypes of diseases is important for the evaluation of animal models.
However, unlike the well-developed testing platforms for rodent models, currently, the evaluation criteria
for rabbit NDD models are not well established.

In general, the diagnosis, prognosis, and autopsy criteria in human NDDs can be used in animal models.
Such investigations can provide data that are comparable to human clinical reports and have better
referential value. Indeed, commercialized analysis platforms, such as serological testing, enzyme-linked
immunosorbent assay, MRI, electromyography, and histological analysis, are versatile and authentic tools
for the assessment of both humans and animals including rabbits. However, it is impossible to apply the
whole set of human diagnostic criteria to animals. For example, the investigation methods for behavioral
and cognitive analyses in humans are hard to apply in animal models. Standardized and species-specific
behavioral analysis platforms can support the assessment of animal disease models. For rodents, systematic
behavioral analysis systems are well established and standardized; systems such as multivariate concentric
[106]
square field and cylinder test are used to investigate traits such as sensory-motor function . In contrast,
the behavioral and cognitive analysis platforms for rabbits are not well developed at present, and further
development of these systems is necessary for the future use of rabbits in neurological disease modeling.

CONCLUSION
Collectively, rabbits are more similar to humans in brain development, with more genetic similarities than
rodents, and longer lifespan and larger body size, suggesting that rabbits can perform well in human
neurological disease modeling in addition to traditional non-human primates, large animals, and rodent
models. Therefore, it is expected that, in the near future, with the further development of genome editing
technology and the establishment of phenotype assessment platforms for rabbit models, the value of rabbits
in the research of neurological diseases can be maximized, not only for the understanding of pathological
mechanisms but also for innovation of therapeutic approaches.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Zhang Z, Song Y