Animal models of neurological diseases have evolved from phenotype-based systems to integrated platforms that link genetics, molecular signaling, synaptic physiology, neural circuits, behavior, and therapeutic responses. Simultaneously, increasingly precise phenotyping has revealed that experimental outcomes are strongly influenced by age, microbiological status, diet, housing, stress, previous experience, health status, and measurement methodology. This review considers these two developments to be complementary requirements for reliable experimental neuroscience. Studies on voltage-gated calcium channel mutants have shown that defined genetic alterations can produce age-dependent abnormalities in motor function, cognition, emotion, autonomic regulation, and seizure susceptibility. Studies on N-methyl-D-aspartate (NMDA) receptor-Calcium-calmodulin-dependent protein kinase II (CaMKII) signaling, epigenetic regulators, stress-related phenotypes, and fear memory circuits have further illustrated how animal models can be characterized across levels, from molecular mechanisms to neural ensembles and therapeutic rescues. Translation to common marmosets extends these approaches to primate sleep and epilepsy, while highlighting the effects of genetic diversity, spontaneous disease, handling, and colony management. In parallel, studies on germ-free animals, diet, the gut microbiota, barrier facilities, cage enrichment, telemetry, and veterinary monitoring have demonstrated that husbandry variables, rather than technical background, are biological determinants. Integrating rigorous disease model characterization with evidence-based husbandry, environmental control, and transparent reporting should improve the reproducibility and translational value of preclinical neuroscience research and the welfare of the animals used.
Murine coronavirus, commonly known as mouse hepatitis virus (MHV), is a representative pathogenic virus in mice. MHV infection in mice is used as a model for viral infections and is utilized to analyze the mechanisms of protection and transmission. By establishing MHV-specific T cell clones and conducting adoptive transfer experiments in infected mice, it was demonstrated that T cells play a crucial role in the protection against MHV infection and that cytotoxic T lymphocytes induce apoptosis in infected cells and suppress viral production. Furthermore, studies using IFN-γ-deficient C57BL/6 mice demonstrated exacerbation of acute hepatitis, establishment of persistent viral infection, and subsequent death due to subacute granulomatous serositis resembling feline infectious peritonitis in cats, possibly in association with persistent infection and the emergence of immune-escape variants. In contrast, all MHV-infected IFN-γ-deficient BALB/c mice died within a short period due to acute fulminant hepatitis, indicating that genetic background differences significantly influence disease progression. Furthermore, in vitro studies demonstrated that BALB/c mouse hepatocytes are more susceptible to MHV than C57BL/6 mouse hepatocytes. Additionally, the mode of transmission of MHV was experimentally analyzed, and clearly correlated with viral growth in the intestine. Other studies have explored a wide range of topics in relation to MHV infection, including autoimmune responses, genetic susceptibility, and the maintenance of pluripotency in MHV-infected embryonic stem cells. MHV has also been utilized as a surrogate virus for COVID-19 research.
The Kitl/c-Kit signaling axis centrally controls mammalian melanocyte development, survival and cutaneous pigment homeostasis. Most known pathogenic Kitl variants are dominant and usually cause multi-system lesions, with variable phenotypic severity among alleles. Here, we comprehensively characterized a novel spontaneous recessive Kitl mutation in C3H/He mice that induces localized hair graying limited to the forehead, abdomen and paws. Linkage mapping positioned the mutation within a 5.05 Mb interval on chromosome 10, and molecular assays verified an intron 3 IAP retrotransposon insertion driving abnormal splicing and inclusion of a 42-bp cryptic exon. This mutant allele is provisionally designated Kitlm1Yzcm. Mutant hair follicles were morphologically intact yet melanin-free; c-Kit and DCT immunostaining showed undetectable follicular melanocyte lineage signals, suggesting localized hair graying may arise from defective melanoblast colonization or alternative post‑migratory melanocyte defects, rather than impaired melanin synthesis.This novel Kitlm1Yzcmmutant provides a mouse model for investigating mechanisms of localized cutaneous depigmentation and supporting pre‑clinical drug development.
