Laboratory rat biology

Rats are rodents, and their small size and rapid reproductive cycle makes them easy to maintain and breed in the laboratory. These factors have contributed to them becoming widely used laboratory animals, with over 8 million rats used in research worldwide. Both inbred and outbred strains of rat are available, although far fewer different strains in comparison to mice. The rat genome has been sequenced, and transgenic rats have been produced, although they are much less widely used than transgenic mice.

Basic biology and anatomy

Laboratory rats have been selectively bred from the brown Norway rat, (Rattus norvegicus) and retain many of the biological features of this wild rodent, although some morphological and behavioural differences are present (Stryjek et al 20121). Rats share common anatomical features with other terrestrial mammals, including humans, but have evolved some specific adaptations.


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Rats, in common with all rodents, have continuously growing incisor teeth (at a rate of 2-3 mm/week) and can gnaw hard materials easily. Laboratory rats are usually fed a hard, pelleted diet, composed of vegetable materials. Rats have a higher metabolic rate than larger species, and so are usually fed ad lib, but in many strains of the laboratory rat, this often leads to obesity.

Like all rodents, rats have a simple, single-chambered stomach, divided into glandular and non-glandular sections. Rats cannot vomit. Their gastrointestinal tract is similar to other mammals but has a relatively large caecum, in which cellulose is digested. Since the caecum is located at the end of the small intestine, at the junction of the ileum and colon, little absorption of nutrients can occur, so rats ingest faecal pellets containing the material from the caecum (caecotrophy). This adaptation is shown by many laboratory rodents and also by rabbits, and can influence research protocols. For example, drug metabolites can be re-ingested and absorbed, and dietary components may be modified because of the addition of this further source of nutrients.

Special senses

Olfaction in rats is highly developed, and they use a wide array of chemical signals to gain information on the environment and on conspecifics. These may be both species-related molecules (pheromones) and mixtures of chemicals specific to an individual animal (Burn, 20082). Rats excrete these signalling molecules in various body fluids (urine, tears, saliva, milk, and possibly other fluids) with urine being the most extensively studied. The emission of these chemical signals may modify the behaviour and/or the physiology of other animals, for example, aggression and attraction towards other rats.

Rats have a well-developed auditory system, with a hearing range of around 0.25-80kHz (human hearing range is approximately 20Hz to 20kHz) depending upon the intensity of the sound (Heffner et al, 19943). Since rats can hear ultrasonic frequencies, it is important to identify sources of loud sounds in this frequency range in the animals’ environment. For example, computer monitors, air conditioning units and activities such as filling food hoppers can produce ultrasound at intensities of 60-90dB. It should also be appreciated that although rats vocalize at frequencies within the range audible to humans, they also make extensive ultrasonic calls.

Rats are very sensitive to touch and have an extensive area of their sensory cortex devoted to processing information from their whiskers and from the nose, mouth and forepaws. They make extensive use of sensory information to navigate and explore their environment and they are extremely sensitive to tactile cues (Hartmann, 20114).

The rat visual system is well developed but visual acuity in laboratory rats is poor in many strains as they rely primarily on olfaction, hearing, and their whiskers to sense their environment (Prusky et al, 20025). Lighting levels in animal facilities that are appropriate for human activities cause retinal atrophy in rats, particularly in albino strains (Organisciak and Winkler, 20016). Rats have a degree of colour vision, ranging from 400nm (ultraviolet) to 635nm (orange-red). Using red-light to observe rats on the assumption that they cannot detect this wavelength may not be completely effective since the rod cells in the retina are responsive to red light at these wavelengths (Leinonen and Tanila, 20177 and Dauchy et al, 20158).

Behaviour

Rats are generally social animals but can show aggression, particularly towards unfamiliar animals. If housed together in single-sex groups (to prevent unwanted breeding) from shortly after weaning, stable social groups generally form. Although these can break down and fighting may occur, injuries are usually minor, and aggression between cage mates is generally much less of a welfare problem than with mice.

Rats are most active during the dark phase of their photoperiod, and also consume most food and water during this period. They actively scent mark their environment, and olfaction plays a major role in communication, the establishment of social hierarchies and in their reproductive behaviour (Roberts, 20079).

Rats actively explore their cage environment and climb and burrow if given appropriate substrates. They will also make use of housing structures placed in their cages. Providing a reasonably complex and enriched environment, which facilitates these normal behaviours, improves the welfare of caged rats and is easily achievable in a laboratory environment (Abou-Ismail et al, 201110, Hutchinson et al, 200511). It is important to note that environmental enrichment has significant effects on many aspects of rodent behaviour and physiology, so its use should be considered when designing research studies (Simpson and Kelly, 201112).

Reproductive biology

Rats become sexually mature at 6-7 week of age. Females have an oestrus cycle lasting 4-5 days. Mating usually results on the formation of a “vaginal plug” of material produced from the male accessory sex glands, and this can be used to confirm mating has taken place. Pregnancy lasts for 21-23 days and varies slightly between different strains. The fetuses can be detected using ultrasound of the abdomen by 9-10 days (Ypsilantis, 200513) and by gentle palpation a few days later. As pregnancy progresses, the abdomen increases in size and the mammary glands, which extend from the inguinal region to the anterior thorax increase in size.

The numbers of pups born varies considerably between strains and can range from only three or four to 16-18, but most rats have 10-16 pups in each litter. Rat pups are born hairless, blind and with the external ears closed, but develop rapidly and are usually weaned at 3-4 weeks of age, depending upon their rate of growth and development (click to see images at 1 day old, 4 days old, 7 days old, 12 days old, 15 days old, 21 days old and 6 months).

Within 24h of giving birth, rats mate again, so large numbers of offspring can be produced very rapidly. To avoid unwanted pregnancies, male and female offspring are housed separately after weaning.

CBC-1727
Fig. 1 Determining the sex is relatively easy, as male rats have an obvious scrotum.

Determining sex is relatively easy, as male rats have an obvious scrotum (Fig. 1). However they have an open inguinal canal, and the testes may be withdrawn back into the abdomen, reducing the size of the scrotum. In younger rats, and in neonates, the sexes are differentiated by the distance between the external genital opening and the anus. This distance is larger in males than in females.

Rat strains

A number of different strains of rat have been developed for use in research, and many of these show variations in their physiology. Some have spontaneous genetic alterations of particular value for specific areas of research, for example, spontaneously hypertensive rats (SHR) develop elevated blood pressure. The different strains of rat are usually categorised as either inbred or outbred. Inbred strains are established and maintained either by brother x sister or father x daughter matings and after approximately 20 generations become almost completely homozygous at all genetic loci. There are far fewer inbred strains of rat than of mice, the most widely used being Fisher 344, and inbred strains of Lewis rats. In contrast to inbred strains, outbred strains such as Sprague Dawley and Wistars show more genetic variation within each strain. Most research studies using mice involve inbred strains, but in rats, outbred strains are more widely used (Festing, 201414).

Transgenic and mutant rats

Transgenic rats have foreign DNA intentionally inserted into their own genes, and this may result in alterations in gene expression – including over and under expression of existing genes, or insertion of new genes. The technology to manipulate the rat genome has become complex and sophisticated, and can now be used to manipulate multiple genetic characteristics rapidly (for example by use of CRISPR/Cas 9 techniques). Extensive information on these techniques can be found in the bibliography at the end of this section.

The phenotype of some GA lines is well established, and the effects on the animals’ welfare will have been identified. It may also be possible to alter housing, husbandry and research procedures to reduce the welfare consequences of the animals’ phenotype. In some circumstances, the effects of the genetic alteration will not have been established. Although it may be possible to predict the impact on the animals’ phenotype, unexpected effects can occur, so careful monitoring will be needed to detect these.

Physiological values

Table: Physiological Values - Rat
Rat
Adult body weight: male250-450g
Adult body weight: female250-300g
Birth weight5-6g
Life span2½-3½ years
Food consumption10g/100g/day
Water consumption10-12ml/100g/day
Breeding onset: male65-110 days
Breeding onset: female65-110 days
Cycle length4-5 days
Gestation period21-23 days
Postpartum estrusFertile
Litter size6-12
Weaning age21 days
Breeding duration350-440 days
Commercial7-10 litters
Note that many of these values vary between different strains of rat, and also vary depending upon housing and husbandry conditions.

Updated on 12th May 2020

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