Inbred strain

Kim CY, Nakai K, Kasanuma Y, Satoh El. 2000. Comparison of neurobehavioral changes in three inbred strains of mice prenatally exposed to methylmercury. Neurotoxicol Teratol 22 397 03. 

Thompson, J. A. Carlson, T. J. Sun, Y. Dwyer-Nield, L. D. Malkinson, A. M. Studies using structural analogs and inbred strain differences to support a role for quinone methide metabolites of butylated hydroxytoluene (BHT) in mouse lung tumor promotion. Toxicology 2001, 160, 197-205. 

Beier DR, Dushkin H, Sussman DJ. Mapping genes in the mouse using single-strand conformation polymorphism analysis of recombinant inbred strains and interspecific crosses. Proc Natl Acad Sci USA 1992 89 9102-9106. 

Kikkawa, Y., Miura, S., Takahama, S., Wakana, S., Yamazaki, Y., Moriwaki, K., Shiroishi, T. and Yonekava, H. (2001) Microsatellite database for MSM/Ms and JFl/Ms, molossinus derived inbred strains. Mammalian Genome 12, 750-752. 

Bennett, K. L., Lalley, P. A., Barth, R. K. and Hastie, N. D. (1982) Mapping the structural genes coding for the major urinary proteins in the mouse combined use of recombinant inbred strains and somatic cell hybrids. Proc. Natl. Acad. Sci. USA 79, 1220-4. 

Fig. 6.1 Different strains of mice detect different concentrations of urinary odours of conspecifics with BALB/c>129/Sl>C57BL/6. Presented are the mean durations ( SEM) that mice investigated water and three sequential 2-min presentations of the same concentration of urine from one of the other strains at (A) 10 2, (B) 10 3 and (C) 10-4 concentrations. Immediatelyafter the presentation of Urine A, mice were exposed to a novel urine B (the other foreign strain) at the same concentration.(Reprinted from Neuroscience, 118, Lee, Emsley, Brown, and Hagg, T. Marked differences in olfactory sensitivity and apparent speed of forebrain neuroblast migration in three inbred strains of mice. 263-270, Copyright (2006), with permission from Elsevier)...

Lee, A.W., Emsley, J.G., Brown, R.E. and Hagg, T. (2003) Marked differences in olfactory sensitivity and apparent speed of forebrain neuroblast migration in three inbred strains of mice. Neurosci. 118,263-270. 

Habert, R. and Picon, R. (1984). Testosterone, dihytrostestosterone and estradiol-17/ levels in maternal and fetal plasma and in fetal testes in the rat. J. Steroid Biochem. 21 183-198. Hansen, D.K. and Hodes, M.E. (1983). Comparative teratogenicity of phenytoin among several inbred strains of mice. Teratology 28 175-179. 

The duration of carcinogenicity studies for both rats and mice is two years in most pharmaceutical laboratories (PMA, 1988). Occasionally, rat studies are extended to 30 months, while some companies terminate mouse studies at 18 months. The difference in duration between mouse and rat studies is based on the behef that rats have a longer natural hfe span than mice. Recent data indicate, however, that this is not the case. The most commonly used strains, the Sprague-Dawley rat and the CD-1 mouse, have approximately equal survival at two years, based on industry data (PMA, 1988). The same is true for the most popular inbred strains, the Fischer 344 rat and the B6C3F1 mouse (PMA, 1988). Data from NCI studies confirm that the two-year survival of the B6C3F1 mouse is at least equal to, if not greater than, that of the Fischer 344 rat (Cameron et al., 1985). 

To a large extent we will have to rely for our information about these vital organs on data pertaining to blood, secretions, and tissues which can be obtained from well individuals without too great inconvenience. Data with respect to animals, if available, would be pertinent but, because of lack of interest in the potential importance of the study of individual differences, there is little material which is directly applicable to our questions. Incidentally, the use of highly inbred strains of animals in laboratory research has resulted in partially wiping out some of the differences which would be most interesting from the standpoint of our study. 

These findings show clearly that even when the animal diets are uniform, highly distinctive urinary excretion patterns are exhibited. The results with different inbred strains show that inheritance is the basic reason for the differences in pattern. It would require extremely extensive genetic studies to demonstrate the inheritance process for each item, but this does not seem crucially important from the standpoint of elucidating the phenomenon of individuality. 

Our evidence leads us to conclude, however, that these patterns tend to remain about the same in reasonably well individuals, at least over a period of years. That very young babies have highly distinctive patterns and that closely inbred strains of rats have close resemblances in their patterns (as do also human identical twins) strongly indicate that the pattern which an adult human being exhibits has not been produced merely as a result of the various illnesses and environmental experiences through which he has passed. 

Further exploration of this line of investigation showed that different colonies of rats and different closely inbred strains are distinctive in their alcohol consumption and in their behavior toward nutritional supplements. The second colony we worked with had a stronger tendency to consume alcohol than the first and was less readily given body wisdom by the administration of available supplements. 

The fact that each inbred strain of animals has not only a distinctive tendency to drink alcohol but also a distinctive excretion pattern makes it seem certain that we are here dealing with individual differences (quantitatively speaking) in nutritional needs. It seems evident that when rats are given plenty of everything they need nutritionally they shun alcohol, and that the reason why some shun it less than others is that their requirements for certain items are higher, and they... 

The genetotrophic idea was first conceived in connection with the experimental work on alcohol consumption by rats. When it was found that the alcohol consumption of rats (1) was highly individual 12, 13, 14 (as were also their excretion patterns), 15 and (2) was genetically controlled (as evidenced by the distinctive behavior of each inbred strain and the relatively small variation within inbred strains),13, 14 and (3) could be increased by deficient diets and abolished by fortified ones, 12, 13 the genetotrophic ideas appeared to be the only reasonable interpretation of the facts. 16,17 Since these original observations were made, dozens of other facts, many of which have been and will be presented in the present volume, have become explicable on the basis of the genetotrophic concept. To date there are no observations, so far as I am aware, that appear to go counter to this idea. 

Even among members of highly inbred strains of rats (brother-sister mated for as long as 50 generations) we have found substantial intrastrain differences in excretion patterns and alcohol-consuming tendencies 18 therefore, it is not surprising that within the strains of... 

Petersen DR, Norris KJ, Thompson JA (1984) A comparative study of the disposition of nicotine and its metabohtes in three inbred strains of mice. Dmg Metab Dispos 12 725-731 Pichard-Garda L, Hyland R, Bauheu J, Eabre JM, Milton A, Maurel P (2000) Human hepatocytes in primary culture predict lack of cytochrome P-450 3A4 induction by eletriptan in vivo. Drug Metab Dispos 28 51-57... 

Stolerman IP, Rauch RJ, Norris EA (1987) Discriminative stimulus effects of a nicotine-midazolam mixture in rats. Psychopharmacology 93 250-256 Stolerman IP, Naylor C, Elmer GI, Goldberg SR (1999) Discrimination and self-administration of nicotine by inbred strains of mice. Psychopharmacology 141 297-306 Stolerman IP, Childs E, Hahn B, Morley A (2002) Drag trace discrimination with nicotine and morphine in rats. Behav Pharmacol 13 49-58... 

The approach of response addition can be easily applied to simple problems, such as acute toxicity of pesticides. However, more complex effects are not always easy to summate. Experimental animals are usually obtained from inbred strains, while human populations are more heterogeneous. In addition, various effects on different organ systems may occur within different time frames in experimental animals. 

There is a continuing debate as to whether inbred or outbred strains of rodents should be used. In theory, inbred strains are preferable because a more accurate knowledge of back-grormd tumour incidence is available. It may be, however, that a particular inbred strain may metabolise the test material in a certain way or have a genetic resistance to the development of a specific tumour type. Usually outbred strains of rat or hamster are used, but occasionally inbred mice strains are included. An FI hybrid mouse strain is frequently employed. In some circumstances outbred Syrian hamsters may be the species of choice. The most important factor is to have a sound knowledge of the background incidence of tumours in the species or strain selected. This information complements the concurrent control data and provides information on the susceptibility of the strain to rare tumour t)rpes. Modif)dng factors, such as diet, cage density, etc., must be kept as constant as possible to enable correct interpretation of the results. ... 

Initial experiments in the 1970s using inbred strains of rats illustrated the feasibility of this approach. Insulin-producing pancreatic islet cells donated by one set of rats were transplanted into other rats of the same strain, first made diabetic by injection with drugs such as streptozotocin, which destroy the pancreatic B cells. 

Gerlai 1996,2001). In such cases, animals have to be crossed with a pure inbred strain (commonly C57BL/6J hnes) for at least 6-8 generations (backcrossing). For correct interpretation of data obtained in genetically modified mice it is indispensable to follow the strict rules of strain nomenclature (Wotjak 2003). 

Brown SDM, Hardisty RE (2003) Mutagenesis strategies for identifying novel loci associated with disease phenotypes. Semin Cell Dev Biol 14 19-24 Cabib S, Puglisi-Allegra S, Ventura R (2002) The contribution of comparative studies in inbred strains of mice to the understanding of the hyperactive phenotype. Behav Brain Res 130 103-109... 

Kopp C, Vogel E, Misslin R (1999) Comparative study of emotional behavior in three inbred strains of mice. Behav Processes 47 161-174... 

Within this context, outbred rats like Wistar or Sprague-Dawley are the most widely used rodents, while New Zealand White or Himalayan rabbits (the latter especially in Europe) are the most frequently used non-rodents. Care should be taken when inbred strains are used, since they may express genetic clusters which can complicate the interpretation of the results. 

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