The thermal biology of laboratory mice encompasses a robust, dynamic, and multifaceted mixture of behavior and physiology. Physical and physiologic adaptations provide the remarkable capacity for mice to survive in temperatures as low as 4 °C and as high as 43 °C. 54,89 Comprehension of these complex systems necessitates a clear definition and solid understanding of the murine thermoneutral zone (TNZ), which is the range of temperatures across which the resting metabolic rate of heat production is at equilibrium with the animal's evaporative heat loss to the surrounding environment. 14,54 Within the TNZ, animals can maintain stable core body temperatures by responsive behaviors, peripheral vessel diameter, and body postures. 54 The overall mouse TNZ is bound by the lower and upper critical temperature limits, beyond which mice must engage in heating or cooling adjustments, respectively; further definition of these critical temperatures is provided in a glossary of terms for thermal physiology. 22 TNZ is determined by body size and weight, morphology, condition, and resting metabolic rate and is particularly narrow in mice, spanning just 1 to 3 °C, because of a large surface-to-volume ratio and meager body insulation (for example, body hair). 54,74,120 These responses to the ambient environment lead to dramatic increases in metabolic rate and alterations in thermal profiles (Figure 1). 14,54 Long-term (chronic) cold-induced exposures for mice often alter experimental results, described across multiple disciplines. 8,10,27,92,118,129 As a result, the biomedical scientific community has asserted the need to account for and better support the thermal biology of mice, 35,40,65,75,92 although dissenting opinions on this matter have been expressed. 127 Unlike many large endotherms, mice do not have stable core temperatures. Their body temperature oscillates over short bursts of approximately 1 °C even within the TNZ. Mice also show circadian fluctuations in their core temperatures and sleep patterns at standard housing temperatures: mice in barren caging conditions at 23.5 °C maintain a core body temperature of 36.2 °C during the light cycle and 37.5 °C during the dark cycle. 48,72 When provided with deep bedding for nesting, light cycle core temperatures increase to an average 37.2 °C, while the dark cycle temperatures remain at 37.5 °C. 48 The mouse's core temperature and related physiologic state should not be attributed to a static number but instead should be viewed as a dynamic value dependent on environmental context. Over many generations of exposure to particular conditions, mice acclimate through the development of anatomic differences based on their rearing temperatures. Mice raised in colder environments grow significantly shorter tails 55 and ears, 4 have longer fur for increased insulation, 4,60 develop larger livers and kidneys 55 and bones, 3 and have larger deposits of brown adipose tissue (BAT) with increased thermogenic capacity. 63,89 The evolutionary strategy of energy conservation through environme...

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The envelope protein is a primary pathogenic determinant for T-cell-tropic feline leukemia virus (FeLV) variants, the best studied of which is the immunodeficiency-inducing virus, 61C. We have previously demonstrated that T-cell-tropic, cytopathic, and syncytium-inducing viruses evolve in cats infected with a relatively avirulent, transmissible form of FeLV, 61E. The envelope gene of an 81T variant, which encoded scattered single-amino-acid changes throughout the envelope as well as a 4-amino-acid insertion in the C-terminal half of the surface unit (SU) of envelope, was sufficient to confer the T-cell-tropic, cytopathic phenotype (J. L. Rohn, M. S. Moser, S. R. Gwynn, D. N. Baldwin, and J. Overbaugh, J. Virol. 72:2686-2696, 1998). In the present study, we examined the role of the 4-amino-acid insertion in determining viral replication and tropism of FeLV-81T. The 4-amino-acid insertion was found to be functionally equivalent to a 6-amino-acid insertion at an identical location in the 61C variant. However, viruses expressing a chimeric 61E/81T SU, containing the insertion together with the N terminus of 61E SU, were found to be replication defective and were impaired in the processing of the envelope precursor into the functional SU and transmembrane (TM) proteins. In approximately 10% of cultured feline T cells (3201) transfected with the 61E/81T envelope chimeras and maintained over time, replication-competent tissue culture-adapted variants were isolated. Compensatory mutations in the SU of the tissue culture-adapted viruses were identified at positions 7 and 375, and each was shown to restore envelope protein processing when combined with the C-terminal 81T insertion. Unexpectedly, these viruses displayed different phenotypes in feline T cells: the virus with a change from glutamine to proline at position 7 acquired a T-cell-tropic, cytopathic phenotype, whereas the virus with a change from valine to leucine at position 375 had slower replication kinetics and caused no cytopathic effects. Given the differences in the replication properties of these viruses, it is noteworthy that the insertion as well as the two single-amino-acid changes all occur outside of predicted FeLV receptor-binding domains.

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