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Mark A. Suckow has 25 years of experience with IACUC organization and regulatory compliance, laboratory animal medicine, research with a variety of animal models, and animal facility design and management. The laboratory rat The Laboratory Rat. Suckow , Steven H. Weisbroth , Craig L. The Laboratory Rat, Second Edition features updated information on a variety of topics including: rat genetics and genomics, both spontaneous and induced disease; state-of-the-art technology for housing and husbandry; occupational health, and experimental models.
By late 18 th or early 19 th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association.
Thus, the current review attempts to compare rat and human age at different phases of their life.
The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity months later.
In adulthood, every day of the animal is approximately equivalent to Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor.
The laboratory rat is an inevitable part of today's biomedical research. They are the laboratory rat as the preeminent model in numerous fields, including neurobehavioral studies, cancer and toxicology. An estimation suggests some dozens of millions per year, being 15 million in the United States, 11 million in Europe, five million in Japan, two million in Canada and less than one million in Australia.
A third group includes rabbits, goats, bulls and in smaller amounts, dogs, cats and some species of primatess. A recent publication dealing with biomedical research applications lists the following areas of biomedical investigation as ones in which the rat is widely used and is particularly useful in: Toxicology, teratology, experimental oncology, experimental gerontology, cardiovascular research, immunology, dental research immunogenetics and experimental parasitology.
Rats have traditionally been the animal of choice in much nutritional research, although it should be noted that their natural habit of coprophagy may limit their suitability for certain of these studies. Their use in scientific research started in the 16 th century, although the development of the laboratory rat as an experimental model really began in when the Wistar Institute developed the Wistar rat model Rattus norvegicus. Rattus rattus was well established in Europe by A.
By the s, these animals were used for neuroanatomy studies in the laboratory rat United States and in Europe. It was in the late s and early s that individual stocks and strains had their beginnings. Today, there are 51 known species of the Rattus of both albino and pigmented types that are available.
There are recognized differences between wild and laboratory rodents. For example, laboratory rats have smaller adrenals and preputial glands, earlier sexual maturity, no reproductive cycle seasonability, better fecundity and a shorter lifespan than their free-ranging wild counterparts.
Numerous methods have been investigated in several studies to correlate the ages of small mammals with that of a human, i.
Several studies have been performed using the weight of the eye lens in an attempt to use the development and growth of the lens throughout the mammalian life as an indicator that could help correlate the ages of different species.
This technique was taken as a useful measure in the late s to correlate the ages of different mammalian species at different stages of life. However, this method proved a useful indicator only up to months; beyond that point, the technique is not precise enough to determine the exact age of the rat.
Some researchers have developed methods to determine the ages of smaller mammals by using the growth of molar teeth, mostly by the molar ageing the laboratory rat or the crown method. The molar of young animals consists solely of a specialized prismatic part i.
In aged animals, most of the crown worns away and the roots are long.
On account of differences in diet and also the laboratory rat primary molar hardness, molar wear may differ geographically; therefore, the molar ageing methods are perhaps not directly applicable outside the area in which they are developed. If accurate assessment of dental development is possible, this method should be given more emphasis in age estimates. In the absence of dental information, assessments of skeletal maturation including long bone lengths and maturation of other skeletal elements can be used.
Although many age determination techniques have been developed, the most widely used method in vertebrates involves a technique of counting endosteal layers in the tibia that allows to accurately determine the age of the experimental animals. It has been reported in several studies that, in younger animals, more lamellae were found than their age in years.
Because dental development is minimal in fetal animals, most estimates of age rely on bone formation, especially long bone lengths, and also other bones such as the assessment of the development of the ilium and the petrous portion of the temporal. If accurate measurements can be taken, formulae exist to allow the calculation of body length and subsequently, the age.
Mostly, bones of the upper and lower limbs and hip joint are used to determine the age of the experimental animal. In the childhood of the animal, closure of metopic suture and appearance of ossific centers are used. In addition, closures of epiphyseal plates are an indicator of the adolescent period. Closures of epiphysis in the bones of the upper limbs wrist, shoulder joint, humerus, ulna, radius, metacarpals and phalanges are found during the age of years of human life, while epiphyseal closure lower limbs femur and the laboratory rat are found during years of age.
In adulthood, every day of the animal is approximately equivalent to By late 18 th or early 19 th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. Thus, the current review attempts to compare rat and human age at different phases of their life. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity months later.
During early adulthood, bone remodeling and maintenance is the prime indicator, while in late adulthood bone wears and tears help in the determination of the animal age; two pubic rami of the hip are found at the age of 6 years, suture at the acetabulum at 15 years, ischeal tuberosity with the ischium at 21 years and iliac crest with the ilium at 23 years. In addition to skeletal measurements and dental evaluation, the extent of formation and union of epiphyses is important. Epiphyseal evaluation involves gross examination in skeletal remains and radiological assessment in fleshed material.
These questions could be answered in various ways. Most of the researchers used to relate human and rat age by simply correlating their life span, which is not acceptable, because, for a specific research work, one uses a particular developmental phase of rat-life.
Thus, one should consider different phases of their life to have the laboratory rat accurate correlation. Laboratory rats live about Thus, one human year almost equals two rat weeks However, while considering the different phases of rat life, including weaning to aged phase, it could be easily noticed that rats have a brief and accelerated childhood in respect of humans.
Rats develop rapidly during infancy and become sexually mature at about 6 weeks of age. Humans, on the other hand, develop slowly and do not hit puberty until about the age of years. Social maturity is obtained in months of age. The unique bond between mammalian mothers and their infants, whom they create and maintain by nursing, is irrevocably broken during weaning.
In a strict sense, the weaning process involves a developmental reorganization of ingestive behavior. Infant altricial mammals subsist entirely on mother's milk; as adults, they independently select and ingest solid foods. Weaning is the transition between these two forms of subsistence, and constitutes an essential element in the progression to adult function in all mammals.
In a the laboratory rat sense, weaning also represents a milestone in the achievement of more global forms of independence, a prominent and universal the laboratory rat in mammalian development that marks a significant change in life pattern.
Weaning or the laboratory rat is the first phase of rat life, which is a developmental process unique to all mammalian young. It is the process of gradually introducing a mammalian infant to an adult diet solid food and withdrawing the supply of its mother's milk [ Table 1 ]. In Rattus norvegicusa species important in laboratory studies of ingestive behavior, the young begin to reliably ingest solid food on about Day 18 P Time spent suckling begins to decline around P20, while time spent ingesting solid food increases.
By about P34, the young no longer suckle and weaning is essentially complete. Therefore, in this developmental phase, one human year equals The second phase of rat-life is its puberty, when reproduction first becomes possible, i. Research on the reproductive physiology using pubertal and adult rats as experimental animal began in the s.
Since then, the species has been more thoroughly characterized in these research fields than any other laboratory animal model.
This biomedical field basically employs pubertal or adult rats. Humans, on the other hand, develop slowly and do not reach puberty until about the average age of Rats, on the other hand, become sexually mature at 6 weeks P This means that rats reach sexual maturity at approximately 38 days i. Thus, in this phase, one human year equals 3.
To determine when an animal is an adult, it is also important to review the developmental stages the animal progresses through to reach adulthood. Both rats and mice show a similar developmental profile [ Figure 1 ]. At P21, rodents are weaned, i. After that, they begin to undergo sexual maturation. This point is reached in female rats at approximately PP34 but, in males, maturity occurs much later at around PP However, the age of sexual maturity varies considerably between individuals, ranging from as the laboratory rat as P40 to as old as P76 in male rats.
Like humans, rats progress through a period of adolescence characterized by behaviors such as increased risk-taking and social play. The body weight of an animal is sometimes considered an indicator of its age. However, weight is not an accurate surrogate marker for age. It has been reported that male rats weighing between g and g differed in age by 3 weeks, from P49 periadolescent to P70 young adulthood.
In addition, male rats of the same exact age showed up to g variation in body weight [ Figure 2 ]. Weight is, therefore, only the laboratory rat approximate marker of age.
Summary. Rats have long been recognized as a valuable biomedical research model, notably in the investigation of aging, toxicology, addiction, and common.
Similarly, to identify adulthood by musculoskeletal maturity with rats is problematic as there is no epiphyseal closure in the long bones.
Thus, during the adolescent phase, Reproductive senescence in female rats occurs between 15 and 20 months of age. During the fertile period in a female's life in most species, mating usually only occurs when a female is fecund at the time of ovulation in spontaneous ovulators or when primed to ovulate in reflex ovulators.
But, this integration of behavior and physiology can break down during aging in female rats. Most aging female rodent exhibits periods of persistent estrus constant sexual receptivity that are associated with the laboratory rat blood titers of estrogen and low levels of progesterone.
Because the tonic estrogen secretion stimulates cornification of the vaginal epithelium, this state is also referred to as persistent vaginal cornification. This is the most common state of acyclicity in laboratory rats. Similarly, the traditional marker of reproductive senescence in women is menopause, characterized by loss of menstrual or fertility cycles at midlife.
Thus, during reproductive senescence, If the periods of post-senescence to death are compared, the following is found: Female rats live an average of days after senescence and female humans live an average of 10, days after senescence. Thus, in the aged phase, Thus, the findings of this review suggest that although rats are indispensable elements of biomedical research,[ 3536373839404142 ] they are not the laboratory rat miniature form of humans;[ 1819 ] differences in anatomy, physiology, development and biological phenomena must be taken into consideration when analyzing the results of any research in rats when age is a crucial factor [ Table 2 ].
Special care should be taken when the intention is to produce correlation with human life. It is important for a researcher to understand that the relative ages are different depending upon the stage of life; therefore, one has to determine the relevant age under investigation and what factors are being analyzed.
For this, special attention is needed to verify the phase in days of the animal and its correlation with age in years of humans. Source of Support: Nil.