of Mice: AKR
. Origin: a dealer named Detwiler in Norristown PA.
Carried by Furth as a high-leukaemia strain from 1928 to 1936, then random
bred at the Rockefeller Inst. for several generations. b x s by Mrs. Rhoades
to F9 then C.Lynch to F21. This strain is best known for it's high incidence
of lymphatic leukaemia, and for the Thy1a
T-cell antigen, which is only present in this and a few other strains.
Early history is obscure, but Acton et al
) found substantial substrain differences, which can best
be accounted for by genetic contamination. This could have occurred at
the time the strain was maintained by random mating. The strain has an
international distribution, ranks about eighth in frequency of use and
is widely used in cancer research for its high leukaemia incidence (Lilly and Pincus, 1973
) and in immunology
as a source of the Thy1.1 (theta AKR) antigen, although this varies between
substrains. Mice of this strain are viraemic from birth and express in
all tissues the ecotropic retrovirus AKV, copies of which are intrgrated
into the genome and which is associated with the development of the leukaemia.
In some substrains additional copies of the viral genomes may be integrated
(Herr and Gilbert 1982
Major substrains include:
Inbr ?. To Jackson Laboratory 1940. Maintained by J.
Inbr ?. To Law 1940, to N 1956 at F53. Maint. by N.
Genetically contaminated and renamed ACR/A. Maint. by A.
Inbr ?. Origin ?. Differs from other substrains in being Mod1a
Oak Ridge, to ?, to Rudale, to Netherlands Cancer Institute 1953. Carries
and appears similar to AKR/J.
Carries an autosomal translocation and has a low fertility (Leonard and DeKnudt, 1967
High intrastrain aggression (2/14) (Southwick
and Clark, 1966
). High food drive (2/15), low emotionality (13/15)
). Long time of immobility
in a forced swimming test (2/9) (Nikulina
et al 1991
) Susceptible to audiogenic seizures (3/11) (Fuller and Sjursen, 1967
). High open-field activity (2/13)
). Low shock avoidance learning
in females (5/6) (Royce et al., 1971
1971). Low preference for sweet tasting substances (saccharin, sucrose,
dulcin and acesulfame, averaged) (24/26) (Lush 1988
Life-span and spontaneous disease
Life-span short (1/22 = 326 days in males, 276 days in females) in conventional
conditions (Storer, 1966). Life-span short (1/17
= 350 days in males, 312 days in females) in fostered SPF conditions (Festing and Blackmore, 1971).
Lymphatic leukaemia 57% in males, 65% in females and 4% in virgin females.
Mammary adenocarcinomas and primary lung tumours less than 1% (Hoag,
1963). Lymphatic leukaemia 66-87% (Festing
and Blackmore, 1971). High gross tumour incidence (1/22) (Storer,
1966). Leukaemia 80-90% in females and 70-80% in males by 18 months
(Nemirovsky and Trainin, 1973). Leukaemia
88% (Myers et al., 1970., 1970). Incidence
of leukaemia not altered by treatment with recombinant human growth hormone
(Bechensteen et al, 1993). Low incidence
of leukemia (about 7% T-cell and 28% B-cell) in the AKR-Fv1b
congenic strain with limited replication and spread of the N-tropic
murine leukemia virus (Rosner et al, 1993, Haran-Ghera et al, 1993).
Normal physiology and biochemistry
Low metabolic rate (18/18) (Storer, 1967). High
concentration of prostaglandin F in epididymis (2/6) (Badr,
1975). Low plasma cholinesterase activity (22/22) (Angel et al., 1967., 1967). Low plasma cholesterol levels
(1/11) (Jiao et al 1990). High N'-methylnicotinamide
oxidase activity in both sexes (2/7) (Huff and
Chaykin, 1967). Low serum haptoglobin levels (11/11) (Peacock et al., 1967., 1967). High hepatic delta-aminolaevulinate
dehydratase activity (1/8) (Doyle and Schimke,
1969). Low serum calcium at 7 months (6/6) (Barrett
et al., 1975., 1975). High porphyrin content in Harderian gland (1/16)
(Margolis, 1971). Venous blood has a high
pH (1/10) (Bernstein, 1966). Blood catalase
has a high specific activity (2/7) (Magdon, 1962).
Resistant to the development of atherosclerosis on a semi-synthetic high
fat diet (cf 5/9) (Nishina et al, 1993).
Sensitive to the development of obesity associated with adipocyte sensitivity
to insulin (contrast SWR/J) (Eberhart et
al, 1994, West et al, 1995). Hyporesponsive
to diets containing high levels of fat and cholesterol (8/9) (Kirk et al, 1995). Eat 30% more calories than SWR (resistant
to high-fat dietary obesity) with a higher fat and lower carbohydrate
intake (Smith et al, 1997).
Low testes weight (8/8) (Shire and Bartke, 1972
Large brain weight in females (13/18) (Storer, 1967
High percent carcass lipid on a high-fat diet (9/9) (West et al 1992
). Large brain weight (3/25) (Roderick et al., 1973
., 1973). Low total leukocyte count
(14/18), high mean corpuscular volume (2/18) (Russell
et al., 1951
., 1951). Large relative thymus weight at 14 days (3/8),
49 days (1/8) and 90 days (1/8) (Albert et
., 1966). Large relative thymus weight (1/6) (Belyaev et al., 1970
., 1970). Low relative spleen weight
(9/9 to 7/9, depending on age) (Albert et
., 1966). A significant number of acinar cells of pancreas
contain up to twelve nuclei (contrast seven other strains, but cf. C58)
). Carries adrenocortical lipid
depletion gene which is characterised by loss of lipid vacuoles and occurrence
of many closely packed mitochondria in cytoplasm of cortical cells (Arnesen, 1963
). Low bone density of femur (8/11)
(Beamer et al, 1996
High susceptibility to transplacental tumour induction by 1-ethyl-1-nitrosourea
(IfS) (Diwan et al., 1973
., 1973). Resistant
to skin ulceration by DMBA (cf. 9/22) (Thomas
et al., 1973
., 1973). Resistant to toxic effects of DMBA (1/6) (Schmid et al., 1966
., 1966). Resistant to
teratogenic effects of 1-ethyl-1-nitrosourea (5/5) (Diwan et al., 1974
., 1974). Resistant to induction of tumours
by 3-methylcholanthrene (10/12) (Whitmire
et al., 1971
., 1971). Highly susceptible to the induction of tumours
by N-Methyl-N-Nitrosourea (MNU) due to a gene on chromosome 7 (Angel et al, 1993
). Sensitive to lethal effects of ozone
(4/21) (Goldstein et al., 1973
but resistant (cf 3/8) to ozone-induced decreases of tracheal potential
(Takahashi et al, 1995
to X-irradiation (19/27) (Roderick, 1963
Resistant to pulmonary hyaline membrane formation in 90% oxygen (2/10)
(Lieberman and Kellog, 1967
incidence of virus-like particles in chemically induced sarcomas (2/6)
but low susceptibility to tumour induction by 3,4-benzpyrene (6/6) (Liebelt et al., 1970
., 1970). Short sleeping
time under hexobarbital anaesthetic (4/15) (Lovell, 1976), short sleeping
time under pentobarbitone anaesthetic (4/23), Lovell (1986
Resistant to colon carcinogenesis by 1,2-dimethylhydrazine (cf. 4/7) (Evans et al., 1977
., 1977). Sensitive to seizures
induced by nicotine (17/19) (Marks et al 1989
Carries gene (Tpmt
) for low levels of thiopurine methyltransferase
activity, catalyzing the S
-methylation of 6-mercaptopurine and
other heterocyclic and aromaticthiol compounds (like C57BL/6, unlike DBA/2)
(Otterness and Weinshilboum 1987a
Airways hyperreactive to acetylcholine (c.f. 3/7) (Zhang et al, 1995
). A diet containing 15% dairy fat, 1% cholesterol
and 0.5% cholic acid did not cause a high incidence of cholesterol gallstones
(like SM, DBA/2 contrast C57L, SWR, A) (Faulkner
et al, 1995
Sensitive to amyloid induction (3/10) but low level of spontaneous amyloid
formation (Ram et al., 1969
., 1969). High
susceptibility to amyloid using Escherichia coli
(Willerson et al., 1969
., 1969). High
lymphocyte phytohaemagglutinin response (11/43) (Heiniger et al., 1975
., 1975). Good immune response to small
doses of bovine gamma-globulin (cf. 4/8) (Levine
and Vaz, 1970
). Poor primary immune response to bacteriophage fd (6/7)
(Klsch et al., 1971
l., 1971). Poor
splenic PFC immune response to pneumococcal polysaccharide (8/9) (Amsbaugh et al. 1972
. 1972). Good immune response to ovomucoid,
but poor response to ovalbumin (cf. 5/12) (Vaz
et al., 1971
., 1971). Good immune response to DNP-keyhole limpet haemocyanin
(2/11) (Borel and Kilham, 1974
between `H' and `L' sheep RBC (cf. 12/18) (McCarthy
and Dutton, 1975
). High susceptibility to IgE-mediated passive cutaneous
anaphylaxis (1/12) (De Souza et al., 1974
1974). Susceptible to the anaphylactic death following an intravenous
injection of bovine serum albumin into primed mice (Lei
et al, 1996
Erythrocytes have a high agglutinability (cf. 14/25) (Rubinstein et al., 1974., 1974). High incidence of expression
of RNA tumour virus group specific antigen (1/5) (Diwan
et al., 1973., 1973). Low immune response to ferritin (14/16) (Young et al., 1976., 1976). Low immune response
to dextran (cf. 6/10) (Blomberg et al.,
1972., 1972). Low immune response to ganglio-series gangliosides (c.f.
4/10) Kawashima et al (1992). Resistant
to immunosuppression of contact hypersensitivity by ultraviolet B light
(cf 4/18) (Noonan and Hoffman, 1994).
High expression of neutral glycosphingolipid GgOse(4)Cer in concanavalin
A stimulated T lymphoblasts (cf 3/6) (Muthing,
Resistant to infection by the obligate intracelluar parasite Besnotia
(1/8) (Lunde and Gelderman,
). Susceptible to a natural intestinal helminth infection (10/10)
). Susceptible to Herpes simplex
infection (11/11) (Lopez, 1975
). Low mortality
in a natural epizootic of ectromelia (8/8) (Briody,
). Resistant to induction of diabetes mellitus by encephalomyocarditis
virus (cf. 7/14) (Boucher et al., 1975
1975). Resistant (1/7) to the induction of dental caries due to infection
with Streptococcus mutans
et al 1991
). Susceptible to infection with murine herpes virus (1/4)
(Kapoor et al 1992
). Mouse mammary tumor
proviral loci have been identified by Lee and Eicher (1990
). Develop severe lesions (1/8) following infection with
(Ashman et al, 1993
Resistant (4/10) to infection with Ehrlichia risticii
(Williams and Timoney, 1994
). Resistant, with low amylase
response to the fungus Paracoccidioides brasiliensis
(Xidieh et al, 1994
). Infection with larval
by transportal injection of hyatid
homogenate results in well developed protoscoleces (cf 4/9) (Nakaya et al, 1997
). Develop paralysis (age-dependent polyomyelitis)
following infection with the lactate dehydrogenase-elevating virus in
common with other mouse strains (e.g. C58) which possess N-tropic ecotropic
murine leukemia proviruses and are homozygous Fv-1n (Anderson et al, 1995
Poor reproductive performance (22/25), output 0.74 young/female/week, litter
size low (22/25) at 4.1 weaned (Festing, 1976a). Intermediate breeding
performance (14/24) (Hansen et al., 1973
1973). Low post-implantation loss of embryos (1/8), but high pre-implantation
losses (8/8) (Leonard et al., 1971
Recommended host for transplantable lymphatic leukaemia BW5147 (Kaliss,
1972). High spontaneous mutation rate (4/21) (Schlager
and Dickie, 1967
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Updated 9 Apr. 1998
MRC Toxicology Unit, Hodgkin Building,
University of Leicester,