As we approach the end of 2024, we would like to briefly summarize recent and forthcoming efforts to streamline the submission and review processes for authors while ensuring that AALAS journals continue to reflect and promote excellence in the ethical conduct of animal research.In addition, we will touch on the important issues of open access and public access, which will require some changes in AALAS policies no later than October 2025 when NIH is expected to require immediate public access to NIH-funded articles accepted for publication in the Journal of the American Association for Laboratory Animal Science (JAALAS).10 Merger of Comparative Medicine (CM) into JAALASAs first announced by editorial in the July 2024 issue of JAALAS 13 (repeated in the August 2024 issue of CM), no new submissions to CM were accepted after August 15, 2024.
The use of analgesia in bacterial challenge models has been met with some controversy in the literature. Several publications suggest that the use of analgesics in infection models can interfere with the host immune response, change microenvironments subsequently altering bacterial pathogenesis, and directly act as an antimicrobial as was reported with opioids such as morphine. Any such interactions would compromise the experimental results, deterring researchers from the use of analgesia. Herein, we address the possible effect of analgesics on bacterial colonization in a Staphylococcus aureus surgical site infection model in Göttingen minipigs. Retrospectively, an expanded analgesia protocol (buprenorphine presurgery and carprofen postsurgery) was compared with a standard analgesia protocol using buprenorphine alone just before surgery. When examined statistically, the expanded analgesia protocol group was noninferior to the standard analgesia protocol group indicating there was no substantial decrease in bacterial burden when an expanded analgesia protocol was administered. Our results highlight the importance of studying the use of analgesia in all animal models of infection to determine if the analgesics will affect experimental outcomes.
Enterovirus D68 (EV-D68) causes severe respiratory disease and is a strong candidate as the etiologic agent of acute flaccid myelitis. Acute flaccid myelitis is a rare neurologic disorder that typically affects adolescents less than 13 y old, manifesting as muscle paralysis or weakness. No approved antiviral compounds or vaccines exist for EV-D68. An appropriate mouse model is needed to develop therapeutics. We previously showed that the AG129 mouse strain, which has a double knockout of Ifnar1 and Ifngr1 on the 129/Sv genetic background, exhibits clear clinical signs when infected intraperitoneally with EV-D68 at postnatal day 10. The AGB6 strain, which has the same double knockout, but on the C57BL/6 (B6) genetic background, is more sensitive to dengue virus infections relative to AG129. Given the widespread use of the B6 background in mouse research, we systematically assessed EV-D68 infection in AGB6, the AB6 and GB6 strains, which have single knockouts in Ifnar1 and Ifngr1, respectively, and the parental B6 strain. AGB6 was highly susceptible to EV-D68, equivalent to AG129. No differences in susceptibility were observed between AGB6 and AB6 and GB6 and B6, suggesting that the IFNγ receptor contributes little to EV-D68 protection. Because B6 is the genetic background for many genetically modified mice, AGB6 facilitates the evaluation of the role of host genes in EV-D68 pathogenesis through genetic crosses. We introduced the knockout allele of Setd3, a gene essential for enterovirus RNA replication, into AGB6. While EV-D68 lethality was completely penetrant in AGB6-Setd3+/+ and AGB6-Setd3+/− mice, all AGB6-Setd3−/− littermates survived until the experimental endpoint. We conclude that AGB6 is well suited for testing EV-D68 therapeutics. Our study further underscores the importance of SETD3 being a promising therapeutic target for controlling EV-D68 and other enterovirus infections.
The congenic BALB/c-crup (‘crup’ meaning ‘cruza-pernas’ in Portuguese or cross legs in English), a homozygous recessive mutant mouse derived from N-ethyl-N-nitrosourea mutagenesis, exhibits a unique phenotype characterized by hindlimb crossing when the mouse is suspended by its tail, along with age-related neuromotor issues. The study aimed to identify the genetic mutation causing the BALB/c-crup phenotype and evaluate the behavioral responses of the mice. Open field test, elevated plus maze, and elevated beam experiments were conducted to evaluate general activity, motor function, as well as sensorimotor and autonomic nervous systems. Genetic mapping and exome analysis identified a nonsynonymous (missense mutation), a single nucleotide variant, in the Taf15 gene. This mutation results in the p.G55S substitution, where glycine is replaced by serine at position 55 in the gene product. Longitudinal assessment by the open field test revealed altered locomotion, decreased mobility, and reduced rearing and grooming frequency in mutant mice. Sensorimotor function declines were observed through reduced surface righting reflex scores, grip strength, and increased hindquarter angle. In the elevated beam test, mutants exhibited tail hypotonia and aversion to traversing the beam. The elevated plus maze revealed altered behavior in closed arms, suggesting increased anxiety-like behavior or sensorimotor impairment. Our findings provide insights into neurologic and behavioral anomalies associated with a Taf15 gene mutation. The altered locomotion, sensory impairments, and disorientation observed in the crup phenotype indicate a progressive neuromotor condition, potentially serving as a novel mouse model for neurodegenerative diseases.
