It is well known that different strains and stocks of laboratory rat are not identical or even very similar e.g. in their physiology, behaviour and biochemical characteristics.
Examples of reported differences between strains and stocks can be seen in Table 1.5. At least some of these differences can be attributed to their genetic background. Indeed, some studies claim that these variables could be used for the quantitative trait loci (QTL) analysis of inbred strains (Lipman et al. 1999, Avsaroglu et al. 2007). QTL analysis is a statistical method for evaluating the alleles that occur in a locus and the phenotypes which they control.
Festing et al. (2002) suggested that by studying various defined genotypes with a factorial design for evaluating the strains, then better precision and applicability within the species could be achieved. Brown Norway (BN) and Fisher 344 (F344) strains differ in various aspects of their physiology, biochemical characteristics and behaviour (Table 1.6). These two strains are commonly used in aging studies (Spangler et al. 1994, Lipman et al. 1996, Lipman et al. 1999, Sheridan et al. 2007). Sheridan et al. (2007) stated the BN and F344 rats are useful models for investigation of the molecular mechanisms because they have the same kind of
interindividual variation in collateral growth capacity and a similar impact of age on compensation as in clinical observations.
Both BN and F344 rats develop spontaneous lesions at older ages. Lipmann et al. (1999) detected 80 and 58 different types of lesions in BN and F344 rats, respectively.
The frequency of lesions was highest in adrenal glands, kidneys, lungs and pancreas in BN rats and in eyes, heart, lungs and kidneys in F344 rats. In addition, the F344 rats had higher incidence for leukaemia.
Van den Brant et al. (1999) studied blood pressure, HR and activity in six inbred rat strains, and they categorised F344 as a
“hypertensive” and the BN as a “hypotensive”
rat strain compared to wild rats. The difference in day-night activity of BN rats was also lower compared to F344 and van den Brant and co-workers concluded that the BN strain no longer possessed the typical rodent nocturnal activity. However, in a study of nest building behaviour (Jegstrup et al. 2005) it was revealed that there was a closer genetic relationship between BN and wild rats than was the case with the two other strains studied (BDIX and LEW). On the other hand, F344 rats have been considered to be ”stress hyper-responsive” because of their high corticosterone responses to restraint and in behavioural studies (Dhabhar et al. 1995).
Kuopio Univ. Publ. C. Nat. and Environ. Sci. 258:1-52 (2009) 39 Table 1.5 Summary of differences in laboratory rat strains and stocks. Abbreviations: BP = blood pressure, HR = heart rate, ACTH = adrenocorticotropic hormone, CBG = corticosteroid-binding globulin, CRF = corticotropin-releasing factor, GR = glucocorticoid receptor, MR = mineralocorticoid receptor, HPA = hypothalamic-pituitary-adrenal. Strains and stocks: BN = Brown Norway, DA = Dark Agouti, F344 = Fischer 344, LE = Long Evans, Lew = Lewis, SD = Sprague Dawley, SHR = Spontaneously Hypertensive Rat, WIST = Wistar, WKY = Wistar-Kyoto, WF = Wistar-Furth.
Study Strains/stocks Topic
Armario et al. 1995 BN, F344, Lew, SHR, WKY
Behavioural and endocrine response to forced swimming stress
Avsaroglu et al. 2007 ACI, BN, COP, F344, Lew, SHR, WAG, WKY
Response to anaesthetics and analgesics
Bean et al. 2008 F344, LE Housing density Behmoaras et al. 2005 LE, F344, WF, WAG,
BN, Lew, LOU
Aortic elastin and collagen
Dhabhar et al. 1993 F344, Lew, SD Plasma CBG and corticosterone, and adrenal receptor activation response to stress Dhabhar et al. 1995 F344, Lew, SD Plasma ACTH, CBG and corticosterone,
and adrenal receptor activation response to stress
Duclos et al. 2005 BN, F344, Lew HPA-axis activity
Glowa et al. 1992 F344, Lew, SD Serum corticosterone response to acoustic stimuli
Gómez et al. 1996 BN, F344, Lew, SHR, WKY
HPA response to chronic stress Gómez et al. 1998 BN, F344, Lew, SHR,
WKY
Glucocorticoid feedback on HPA-axis Irvine et al. 1997 SHR, WKY Influence of restraint on BP
Jegstrup et al. 2005 BN, BDIX, Lew Nest-building behaviour
Lemaire & Mormède 1995 WIST, LE, BHR BP and HR during chronic social stress Lipman et al. 1996 BN, F1(F344 x BN),
F1(BN x F344)
Pathologic characterisation Lipman et al. 1999 BN, F344, F1(BN x
F344)
Effect of genotype and diet on age-related lesions
Marissal-Arvy et al. 1999 BN, F344 Corticosteroid receptor efficiency and regulation
Marissal-Arvy &
Mormède 2004
BN, F344 Excretion of electrolytes Nemelka et al. 2008 F344, LE Housing density
Ohtsuka et al. 1997 BN, F344 Response to formaldehyde inhalation
40 Kuopio Univ. Publ. C. Nat. and Environ. Sci. 258:1-52 (2009) Study Strains/stocks Topic
Prusky et al. 2002 DA, F344, F1(F344 x BN), LE, SD, WIST, wild
Visual acuity
Ramos et al. 1997 SHR, WKY, BN, WF, F344, Lew
Anxiety-related behaviour Rex et al. 1996 WIST, Lew, F344,
BN
Fear-motivated behaviour Rosenberg et al. 1987 Lew, BN, F1(Lew x
BN)
Sleep Sarrieau & Mormède
1998
BN, F344 HPA-axis activity Sarrieau et al. 1998 WIST, BN, F344,
F1(BN x F344)
Neuroendocrine response to stress Sharp et al. 2005b SD, SHR HR, BP and activity
Sheridan et al. 2007 BN, F344, F1(F344 x BN)
Aging and mesenteric collateral growth Spangler et al. 1994 BN, F344, F1(F344 x
BN)
Behavioural assessment of aging Sternberg et al. 1992 F344, Lew, SD Plasma ACTH and corticosterone and
hypothalamic CRF response to behavioural and restraint stress
Tordoff et al. 2008 14 stocks and strains 17 taste compounds
van de Weerd et al. 1996 WIST, BN Preference for flooring types van den Brant et al. 1999 BB, BN, LEW, DA,
F344, WKY, wild
HR, BP and activity van den Buuse 1994 SHR, WKY HR, BP and activity van der Staay & Blokland
1996
WIST, BN, F344, F1(F344 x BN)
Behavioural tests Webb et al. 2003 F344, Lew, LE, SD,
WIST
Morphology, sensorimotor and locomotor abilities
Kuopio Univ. Publ. C. Nat. and Environ. Sci. 258:1-52 (2009) 41 Table 1.6 Summary of verified differences between BN and F344 rats. Abbreviations: GR = glucocorticoid receptor, MR = mineralocorticoid receptor, SBP = systolic blood pressure, DBP = diastolic blood pressure, HR = heart rate.
Study Topic Main Results/Differences
Armario et al. 1995 Forced swimming behaviour BN less struggling and more immobile / F344 higher corticosterone levels Avsaroglu et al. 2007 Response to anaesthetics and
analgesics
Both strains resistant to medetomidine / BN hypersensitive to ketamine / F344s had longer sleep time with all anaesthetics studied
Duclos et al. 2005 HPA-axis activity F344 corticosterone level higher / BN more active with running wheel Gómez et al. 1996 HPA response to chronic
stress
BN higher increase in ACTH after immobilization
Gómez et al. 1998 Glucocorticoid feedback on HPA-axis
F344s higher MR and GR levels in hippocampus and pituitary
Lipman et al. 1996 Pathologic characterisation BN lower pathology and higher longevity Lipman et al. 1999 Effect of genotype and diet
on age-related lesions
BN had more kidney related lesions / F344 liver and eye related lesions Marissal-Arvy et al.
1999
Corticosteroid receptor efficiencies and regulation
F344s higher MR levels in hippocampus and pituitary /
BNs higher GR levels in hypothalamus Marissal-Arvy &
Mormède 2004
Excretion of electrolytes No differences of urinary of Na+ and K+ / BN higher preference for saline
Ohtsuka et al. 1997 Response to formaldehyde inhalation
BN less sensitive to formaldehyde Ramos et al. 1997 Multiple test of
anxiety-related behaviours
BN less anxiety-related behaviours Rex et al. 1996 Fear-motivated behaviour BN more active and explorative in the
open field Sarrieau & Morméde
1998
Activity of HPA-axis BN adrenals larger / F344 corticosterone higher / Plasma transcortin level twice that of F344 / Higher density of MR in F344 Sarrieau et al. 1998 Genetic factors involved in
neuroendocrine response to stress
BN adrenals larger / F344 corticosterone level higher / BN ACTH higher / F344
prolactin and renin activity higher Sheridan et al. 2007 Mesenteric collateral growth
capacity
BN collateral growth at a younger age
42 Kuopio Univ. Publ. C. Nat. and Environ. Sci. 258:1-52 (2009) Study Topic Main Results/Differences
Spangler et al. 1994 Behavioural assessment of aging
F344 more active / F344 worse muscular strength and coordination / F344 worse learning / F344 higher number of lesions (at two years of age)
Tordoff et al. 2008 Preference for taste compounds
F344 preferred tasty compounds Van den Brant et al.
1999
Blood pressure, HR and LA F344 higher SBP, DBP, HR and night time motor activity
Van der Staay &
Blokland 1996
Behavioural differences F344 less explorative both in the open field and light-dark box / BN better spatial discrimination performance /
F344 better shock sensitivity