The daily clock keeps ticking without melatonin
The suprachiasmatic nucleus, or SCN, is the brain's central clock. It receives light information from the retina and coordinates daily rhythms in behavior and physiology. Comparing mice with a fully working melatonin system against mice that produce too little melatonin or lack the MT1 and MT2 receptors showed that an intact melatonin system is not needed to generate or maintain rhythmic behavior under ordinary, entrained conditions [1]. In other words, the clock runs on its own; melatonin is not the motor.
That does not make melatonin irrelevant. The same comparisons indicated that the body's own melatonin stabilizes locomotor activity when animals are kept on a regular light-dark cycle, although the effect is subtle [1]. The subtlety matters: it suggests other signals, such as corticosterone or temperature, also help synchronize activity [1]. A strain difference here is a difference in fine-tuning, not in whether a rhythm exists.
After a light shift, melatonin-competent mice adapt faster
The clearest behavioral difference appears when the light schedule is abruptly shifted, as in jet-lag experiments. Mice with an intact melatonin system re-entrained their locomotor activity sooner, and their molecular clock in the SCN adapted more rapidly [1]. The effect depended on the MT2 receptor, one of the two main melatonin receptors [1].
This is a case where the strain comparison changes the conclusion you would draw. If you only studied melatonin-deficient mice, you could conclude that melatonin plays no role in circadian timing. Adding melatonin-competent mice shows that melatonin speeds up adjustment to a changed light schedule, even though it is dispensable for keeping time under steady conditions [1]. The same pattern is described in a review of mouse models: melatonin is not necessary for the SCN clock rhythm, but it has distinct effects on light-driven synchronization and on re-entrainment to phase advances via MT2 [2].
For seasonal biology, the strain choice is decisive
Seasonal functions run through a different structure, the hypophysial pars tuberalis (PT), a small gland region that relays day-length information. Here melatonin is not a subtle modulator but an essential driver: through the MT1 receptor it drives the PT's own molecular clock and the output pathways controlling seasonal rhythmicity [2]. The contrast with the SCN is stark, and it means a melatonin-deficient strain is poorly suited to studying this seasonal circuitry.
A practical consequence follows. Inbred and transgenic mice do not show seasonal reproduction, but the PT pathways are fully intact if the animals are melatonin-proficient, which is why only melatonin-proficient strains are considered suitable for investigating the circadian and melatoninergic systems [2]. A study of melatonin-competent mice raised under long versus short photoperiods found widespread changes in SCN gene expression, including shifts in the timing of gene rhythms and altered expression of light-response and neuropeptide signaling genes [3]. That work describes photoperiod plasticity in mice with an intact melatonin system; it does not itself compare strains, so it shows what such mice can reveal rather than settling the strain question.
What this means if you are reading or designing a study
The strain you choose sets the question you can answer. Melatonin-deficient mice are a reasonable model for asking whether a rhythm can exist without melatonin, and the answer is yes for the core SCN clock and for rhythmic behavior under entrained conditions [1]. Melatonin-competent mice are needed to ask how melatonin sharpens timing: faster re-entrainment after a light shift, more stable activity, and intact seasonal signaling through the PT [1][2].
One more finding points beyond timing. The comparison between mice with intact and compromised melatonin systems also suggests effects on sleep, memory, and metabolism [1]. Those are presented as leads rather than settled results, and the circadian effects themselves are described as subtle, so the honest summary is that strain differences matter most for questions about adjustment and seasonal control, and least for whether a daily rhythm exists at all [1].
Sources used in this answer
The Role of the Melatoninergic System in Circadian and Seasonal Rhythms—Insights From Different Mouse Strains
Comparing mouse strains with intact versus compromised melatonin systems shows melatonin is not required for generating or maintaining rhythmic behavior under entrained conditions, but it facilitates faster re-entrainment via MT2, stabilizes locomotor activity subtly, and supports seasonal chronotype plasticity.
Mouse Models in Circadian Rhythm and Melatonin Research
Melatonin is not necessary for the SCN molecular clock rhythm but has distinct effects on light synchronization and MT2-dependent re-entrainment, while being essential for pars tuberalis function, so only melatonin-proficient strains are suited to investigate circadian and melatoninergic systems.
Transcriptomic Plasticity of the Circadian Clock in Response to Photoperiod: A Study in Male Melatonin-Competent Mice
In melatonin-competent mice raised under long versus short photoperiods, SCN transcriptomic profiling revealed fewer rhythmic genes under long photoperiod, generally advanced gene expression timing, and altered light-response and neuropeptide signaling genes as candidate mechanisms of photoperiod plasticity.
Weekly and seasonal variation in the circadian melatonin rhythm in humans: A response
Human dim light melatonin onset data suggest a roughly one-hour earlier melatonin rise in summer, interpreted as a combined result of daylight saving time-induced behavioral advances and stronger natural light exposure in summer.
Melatonin, circadian rhythms and glaucoma: current perspective
In primary open-angle glaucoma, circadian rhythms and salivary melatonin timing and amplitude are altered, particularly in advanced disease and in carriers of the MTNR1B rs10830963 G-allele, and oral melatonin improved circadian alignment of body temperature and intraocular pressure in a pilot study.