Inbred Strains
of Rats: WAG
Inbr. 138.
Colour: Albino,
Genet. a, c, h or H, depending on subline; most commonly a,
c, h.
Origin: AL Bacharach, Glaxo Ltd 1924 from Wistar stock. Note that the presence
of different coat color alleles in some sublines implies that this strain
may have become genetically contaminated at some time in the past. It
is therefore important that the subline should be stated carefully in
published work. WAG/Cpb clearly differs from other sublines at many loci
(Festing and Bender 1984).
Characteristics
Behaviour
Short latency to emerge from cage into familiar (4/12 males, 3/12 feamles)
and novel environments (2/12 males, 3/12 females) (
Harrington
1971a). High open-field ambulation (2/12) (
Harrington
1972). High wheel activity (2/12) (
Harrington
1971b). Low open-field defecation (7/8) but high ambulation and shock-avoidance
learning (1/8) (
Rick and Fulker 1972).
Biochemistry and physiology
Low brain GABA (Rick et al 1971). Rij substrain
develops spontaneously occurring spike-wave paroxysms on the electroencephalogram,
accompanied by clinical phenomena resembling human 'petit mal' or absence
epilepsy. A second type of novel wave was not associated with any behavioural
correlates and was seen exclusively during wakefulness (van Luijtelaar
and Coenen 1986, Coenen and van Luijtelaar
1987, Coenen et al 1992, van Luijtelaar
and Coenen 1989). The condition appears to be due to more than one dominantly-acting
genes (Peeters et al 1990, 1992), and
follows definite 24 hour rhythms (Van Luijrelaar
and Coenen, 1988), being particularly marked during light slow wave
sleep and passive wakefulness (Drinkenburg et al 1991). The response to
anti-epileptic drugs corresponds to that of human absence epilepsy (Peeters et al 1988). In contrast, the ACI
strain was almost free of spike-wave discharges, while BN/Bi, B and G
were intermediate (Inoue et al 1990). Some
solvents for antiepileptic drugs have proepileptic potencies in this strain
(Peeters et al, 1992). Blockage ofAMPA andkainate receptors led to an
antiepileptic effect without inducing behavioural alterations (Peeters et al, 1994). A low dose of fentanyl (0.01mg/kg)
with fluanisone (0.5 mg/kg) caused a large increase in epileptic activity,
which was larger than with higher doses (Inoue
et al, 1994).
Lifespan and spontaneous disease
Endocardial disease 4% at an average age of 31 months (Boorman et al 1973). Tumours: medullary thyroid carcinoma
27%, chromophobe adenoma of the pituitary 68%, adrenal cortical adenoma
29%, pheochromocytoma 2%, islet cell adenoma 1%. Mean life-span more than
31 months in females and 22 months in males (Boorman
et al 1972). Mean life-span 31 months in females with pituitary tumours
found in 69% of females. Other common tumours include medullary thyroid
carcinoma 40%, adrenal cortical adenoma 29%, fibroadenoma of breast 21%
with 19 other types of tumour found in 290 animals (Boorman and Hollander 1973). 90% survival to 13 months,
50% at 24 months and 10% at 31 months in virgin females, 90% at 23 months,
50% at 29 months and 10% at 38 months in breeding females (Burek
1978). Pancreatic atrophy 16% in females, 11% in males; hydronephrosis
16% in males; cystic ovaries 36% in males (Burek
1978). Bilateral retinal degeneration with early onset and slowly
progressive course which resembles human retinitis pigmentosa (Lai et al 1980). Further details of aging given by Hollander
(1976).
Immunology
Resistant to experimental allergic encephalomyelitis (
Hughes and Stedronska 1973). Some sublines may carry recessive
gene
dx preventing anaphylactoid reaction to dextran (
Harris et al 1963). Susceptible to the induction of autoimmune
thyroiditis (
Rose 1975). Higher incidence of polyspermia
than in PVG (
Braden 1958). Susceible to iron
deficiency. Low secondary antibody esponse to the polypeptide (T,G)-Pro-L
(17/20) (Günther et al 1976). Poor (4/5) antibody response to a synthetic
20 amino acid peptide derived from the alpha helical region of the RT1-D-u
beta chain (
Murphy et al, 1994).
Miscellaneous
High biliary excretion of copper after intravenous injection of CuSO
4
(1/4) (
Nederbragt and Lagerwerf 1986).
Haematological parameters described by Lovell et al (
1981). Long gestation period (1/8) Peters (
1986).
Boorman
G. A., van Noord M. J., and Hollander C. F. (1972) Naturally occurring
medullary thyroid carcinoma in the rat. Arch. Pathol. 94,
35-41.
Boorman
G. A. and Hollander C. F. (1973) Spontaneous lesions in the female WAG/Rij
(Wistar) rat. J. Gerontol. 28, 152-159.
Braden A. W. H. (1958)
Strain differences in the incidence of polyspermia in rats after delayed
mating. Fert. Steril. 9, 243-246.
Burek J. D. (1978) Pathology
of aging rats. CRC Press, West Palm Beach, Florida.
Coenen
A. M. L. and Van Luijtelaar E. L. J. M. (1987) The WAG/Rig rat model for
absence epilepsy: age and sex factors. Epilepsy Res. 1,
297-301.
Coenen
A. M. L., Drinkenberg W. H. I. M., Inoue M., and Van Luijtelaar E. L.
J. M. (1992) Genetic models of absence epilepsy, with emphasis on the
WAG/Rij strain of rats. Epilepsy Res. 12, 75-86.
Festing
M. F. W. and Bender K. (1984) Genetic relationships between inbred strains
of rats. An analysis based on genetic markers at 28 biochemical loci.
Genet. Res. 44, 271-281.
Harrington
G. M. (1971a) Strain differences among rats initiating exploration of
differing environments. Psychon. Sci. 23, 348-349.
Harrington
G. M. (1971b) Strain differences in rotating wheel activity of the rat.
Psychon. Sci. 23, 363-364.
Harrington
G. M. (1972) Strain differences in open-field behavior of the rat. Psychon.
Sci. 27, 51-53.
Harris
J. M., Kalmus H., and West G. B. (1963) Genetical control of the anaphylactoid
reaction in rats. Genet. Res. 4, 346-355.
Hollander C.
F. (1976) Current experience using the laboratory rat in aging studies.
Lab. Animal Sci. 26, 320-328.
Hughes
R. A. C. and Stedronska J. (1973) The susceptibility of rat strains to
experimental allergic encephalomyelitis. Immunol. 24,
879-884.
Inoue M.,
Peeters B. W. M. M., van Luijtelaar E. L. J. M., Vossen J. M. H., and
Coenen A. M. L. (1990) Spontaneous occurrence of spike-wave discharges
in five inbred strains of rats. Physiol. Behav. 48, 199-201.
Inoue M.,
Ates N., Vossen J. M. H., and Coenen A. M. L. (1994) Effects of the neuroleptanalgesic
fentanyl-fluanisone (Hypnorm) on spike-wave discharges in epileptic rats.
Pharmacol. Biochem. Behav. 48, 547-551.
Lai Y.-L., Jacoby
R. O., Jensen J. T., and Yao P. C. (1980) Retinitis pigmentosa. Am.
J. Pathol. 98, 281-284.
Lovell
D. P., Archer R. K., Riley J., and Morgan R. K. (1981) Variation in haematological
parameters among inbred strains. Lab. Anim. 15, 243-249.
Murphy
G., Dalchau R., Parker K. E., Sawyer G. J., Carter C. A., and Fabre J.
W. (1994) T-cell recognition of an allogeneic RT1-dbu class-II
MHC peptide. Immunology Letters 41, 195-199.
Nederbragt
H. and Lagerwerf A. J. (1986) Strain-related patterns of biliary excretion
and hepatic distribution of copper in the rat. Hepatology 6,
601-607.
Peeters
B. W. M. M., Spooren W. P. J. M., Van Luijtelaar E. L. J. M., and Coenen
A. M. L. (1988) The WAG/Rij rat model for absence epilepsy: anticonvulsant
drug evaluation. Neurosci. Res. Commun. 2, 93-97.
Peeters
B. W. M. M., Kerbusch J. M. L., van Luijtelaar E. L. J. M., Vossen J.
M. H., and Coenen A. M. L. (1990) Genetics of absence epilepsy in rats.
Behav. Genet. 20, 453-460.
Peeters
B. W. M. M., Ramakers G. M. J., Vossen J. M. H., and Coenen A. M. L. (1994)
The WAG/Rij rat model for nonconvulsive absence epilepsy - involvement
of non-NMDA receptors. Brain Res. Bull. 33, 709-713.
Peters A. (1986) Length
of gestation period in eight inbred strains and three outbred stocks of
rats. Animal Technology 37, 109-112.
Rick J. T.,
Tunnicliff G., Kerkut G. A., Fulker D. W., Wilcock J., and Broadhurst
P. L. (1971) GAG production in brain cortex related to activity and avoidance
behaviour in eight strains of rat. Brain Res. 32, 234-238.
Rick J. T.
and Fulker D. W. (1972) Some biochemical correlates of inherited behavourial
differences. Prog. Brain Res. 36, 105-112.
Rose N. R. (1975) Differing
responses of inbred rat strains in experimental autoimmune thyroiditis.
Cell. Immunol. 18, 360-364.
Van Luijtelaar
E. L. J. M. and Coenen A. M. L. (1988) Circadian rhythmicity in absence
epilepsy in rats. Epilepsy Res. 2, 331-336.
INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW
Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester,
UK
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