Inbred Strains
of Mice: A
Inbr: More than F150. Albino. Genet:
a, b, c. Origin: Dr L. C.
Strong, 1921, from a cross between the Cold Spring Harbor and Bagg albino
random-bred stocks (and therefore relavted to BALB/c). Internationally
distributed, Strain A was the third most widely used strain in cancer
and immunology research (
Festing, 1969), though
its popularity has probably declined recently. Although it may be classified
as a general-purpose strain, it is well known for a high susceptibility
to induction of congenital cleft palate by cortisone and a high spontaneous
incidence of lung adenomas, as well as developing a high incidence of
lung tumours in response to carcinogens. Shimkin and Stoner (
1975) suggest that this response may be used as a rapid
in
vivo assay for carcinogenesis. The strain also suffers from
a defect in macrophage function somewhat resembling the mutant
lps
found in C3H/HeJ (
Vogel et al 1981).
The following main substrains are recognised, though they have not been
defined by genetic markers:
A/St
Maintained by Strong.
A/He
Strong to Heston, 1938.
A/GrFa
Main British substrain, Strong to Gruneberg 1932, and mainly distributed
by Falconer.
A/WySn
Strong to Bittner 1927, to Wooley, to Snell, 1951.
A/J
Strong to Cloudman 1928, to Jackson Laboratory 1947, now widely distributed.
Behaviour
Low intra-strain aggression (13/14) (
Southwick
and Clark, 1966), low food drive (15/15) and exploratory activity
(15/15) (
Thompson, 1953). Low spontaneous
bar pressing activity (12/14), low open-field activity (13/14 and 14/14
in J and He substrains), low social grooming during aggressive encounters
(12/14 in He substrain) and high tail rattling score (3/14 and 5/14 in
J and He substrains) during aggressive encounters (
Southwick and Clark, 1968). Low spontaneous locomotor activity
(2/9) (
Nikulina et al 1991). High shock
avoidance learning (3/9) (
Bovet et al., 1966.,
1966), high avoidance conditioning (2/9) (
Royce,
1972), and (2/6 males, 1/6 females) (
Royce
et al., 1971., 1971), but poor shock avoidance learning (8/8) (
Wahlsten, 1973), poor T-maze learning (6/6) (
Stasik, 1970). Long latency to attack crickets
(7/7) (
Butler, 1973). Long latency to emerge
from home cage (7/7), low exploration in Y-maze (6/7), low rearing (6/7),
long latency to climb barrier (7/7), low hole-in-the-wall entry (7/7),
low stair climbing (6/7) (
McClearn et al.,
1970., 1970). Poor shock avoidance conditioning (6/7 and 7/7 in He
and J substrains) and rapid extinction (1/7 and 2/7 in J and He substrains)
(
Schlesinger and Wimer, 1967). Poor
performance in a food-seeking task (6/6) (
Henderson,
1970). High social dominance of males in competition for females (1/6)
(De Fries and McClearn, 1970). High open-field defaecation (1/5) in both
sexes (
Bruell, 1969). Low open- field activity
(12/13) (
Bruell, 1964). Low proportion of paradoxical
sleep (6/7) (
Pagel et al., 1973., 1973),
low incidence of tail rattling (5/5) (
St. John, 1973).
High shuttle box avoidance (1/5) (
Messeri
et al., 1972., 1972). Low wheel activity (5/5) (
Messeri et al., 1972., 1972), low alcohol preference (15/18)
(
Rodgers, 1966).
Life-span and spontaneous disease
Primary lung tumours 6% in male, 32% in female and 26% in virgin females
in J substrain; 44% in males, 23% in females and 30% in virgin females
in He substrains (Hoag, 1963). Zero incidence
of lymphatic leukaemia in He substrain, 1% in J substrain. Mammary adenocarcinomata
zero in males, 1% in virgin females, 28% in breeding females of J substrain
and 54% in breeding females of He substrain (Hoag,
1963). Pulmonary tumours 90% in mice at 18 months (Heston,
1963). Leukaemia 3% in HeJ substrain (Myers
et al., 1970., 1970). A high proportion of the mammary tumours are
of the acinar type (3/7) (Tengbergen, 1970).
Lung adenomas 53-64% in BrA and A substrains, but mammary tumours zero
(Muhlbock and Tengbergen, 1971). Lung
tumours 4-31% and lymphatic leukaemia 10-43% (Festing
and Blackmore, 1971). Spontaneous lung tumours occur at rate of 0.21
tumours/mouse at 24 weeks (Poirier et al.,
1975., 1975). Rare spontaneous myoepitheliomas arising from myoepithelial
cells of various exocrine glands have been observed in the J and HeJ
substrains (Sundberg et al 1991)
Life-span in conventional conditions intermediate in both sexes (9/22 =
490 days in males, 13/22 = 590 days in females (Storer, 1966). Life-span
in SPF fostered conditions intermediate (8/17 = 512 days) in males and
short (3/17 = 558 days) in females (Festing
and Blackmore, 1971). Life-span 662 days in males and 688 days in
females (Goodrick, 1975). Median life-span
400 days in HeJ substrain (Curtis, 1971).
Spontaneous congenital cleft palate 4% and high susceptibility to teratogenic
effects of cortisone, which may be associated with the H2a
allele, (Bonner and Slavkin, 1975).
Congenital malformations in new-born mice 10% (1/9), including cleft
lip and palate and polydactyly (Kalter, 1968).
WySn substrain has 20% cranofacial defects due to the action of two genetic
loci with unequal duplicate epistasis (Juriloff,
1995). Cleft palate is a function of foetal genotype rather than maternal
factors (Yoshida et al, 1996). An exclusion
map for the major gene causing nonsyndromic cleft lip with or without
cleft palate has swept 40% of the mouse genome, with candidate regions
on chromosomes 12, 18 and 19 with a few candidate loci (Juriloff,
1993).
Low incidence of virus-like particles in chemically induced sarcomas (6/6)
(Liebelt et al., 1970., 1970). Can be
made obese by a suitable diet (Fenton and
Dowling, 1953). Does not develop non-insulin-dependent diabetes mellitus
and hypertension when fed a high fat-high simple carbohydrate diet, whereas
C57BL/6 mice do (Mills et al 1993). Blood
glucose levels and insulin insensitivity in crosses between diet-induced
type II diabetes sensitive C57BL/6 and resistant A/J are genetically
independent (Surwit et al 1991)
High incidence of amyloidosis (Russell and
Meier, 1966). No amyloidosis found by Powers et al. (1976) in He and HeJ substrains, in contrast to previous
reports. About 4% incidence of congenital open eyelids (Dagg,
1966). High incidence of cannibalism of young restricted to anatomically
defined mutilation and amputation, particularly of neck, lower jaw and
digits in Ha substrain (Hauschka, 1952).
Relatively resistant to secondary amyloidosis which does not appear to
be associated with variation in the serum amyloid A gene cluster (Butler and Whitehead, 1994).
Normal physiology and biochemistry
Low metabolic rate (16/18) (Storer, 1967). High
plasma testosterone level and binding capacity (1/5) (Hampl et al., 1971., 1971). Low Na/K ratio in erythrocytes
(7/9) and plasma (8/9) (Waymouth, 1973). Low
serum ceruloplasmin in males (23/26) but intermediate in females (Meier and MacPike, 1968).
Low systolic blood pressure (17/19) (Schlager
and Weibust, 1967). Low peripheral nerve conduction velocity (5/6)
(Hegmann, 1972). High concentration of prostaglandin
F in epididymis (1/6) (Badr, 1975). High glucose-6-phosphate
dehydrogenase and nicotinamide-adenine dinucleotide phosphate levels in
erythrocytes (1/8) (Erickson, 1974). High
sensitivity to thyrotrophin (2/21) (Levy et
al., 1965., 1965). Mammary gland insensitive to oestradiol and progesterone
(1/7) (Singh et al., 1970., 1970). High
glucose-6-phosphate dehydrogenase activity (1/16) (Hutton,
1971). High brain acetylcholinesterase activity (1/5) (Pryor et al., 1966., 1966).
High rectal (1/9) but low tail temperature (9/9) (Shepard and Habas, 1967). Low serum calcium level at 4 months
of age (6/6) (Barrett et al., 1975.,
1975). Responds by higher growth rate on high fat diets (1/4) (Fenton and Carr, 1951). Low cell turnover as estimated
by slow clearance of DNA-bound radioactivity (16/17 and 15/17 in J and
He substrains, respectively) (Heiniger et
al., 1972., 1972). High erythrocyte catalase level (4/18) (Hoffman and Rechcigl, 1971). Low kidney (11/12) and liver
(10/12) arylsulphatase activity (Daniel, 1976).
High hepatic delta-aminolaevulinic acid synthetase activity after DISC
treatment (4/15 in He substrain, 5/15 in J substrain) (Gross and Hutton, 1971). High basal serum prolactin level
in females of St substrain (2/6) (Sinha et
al., 1975., 1975). Urine has high osmolality (2/7) (Silverstein,
1961). Blood catalase has high specific activity (1/7) (Magdon,
1962). Resistant to the development of atherosclerosis on a semi-synthetic
high fat diet (cf 5/9) (Nishina et al, 1993).
Anatomy
High percent carcass lipid on a high-fat diet (7/9) (
West et al 1992). Small spinal cord (25/25), small brain/body
weight ratio (16/20) (
Roderick et al., 1973.,
1973). Small relative kidney size (20/21) (
Schlager,
1968). Low total leukocyte count (16/18), low erythrocyte count (18/18
J substrain, 17/18 He substrain), low haematocrit (17/18), low haemoglobin
per 100 cm
3 blood (16/18 He substrain, 14/18 J substrain) (
Russell et al., 1951., 1951). Small thymus/body
weight ratio (6/6) (
Belyaev et al., 1970.,
1970). Low proportion acidophilic (5/5) and high proportion chromophobe
cells in adenohypophysis (
Keramidas and
Symeonidis, 1973). High frequency of mast cells in spleen also found
in A.CA and A.SW (1/14) (Vicklicky, 1967). Low yield of peritoneal exudate
cells (5/5) with low percentage of macrophages (5/5) and granulocytes
(5/5) but high percentage of lymphocytes (1/5) (
Schwartz et al., 1975., 1975). Adrenal gland has a high incidence
of vacuolisation of the X-zone (1/6) (
Delost
and Chirvan-Nia, 1958). Small pituitary (6/6) (
Sinha et al., 1975., 1975). Number of nipples commonly less
than five pairs. Small number of Peyer's patches (6/7) (
Hummel et al., 1966., 1966). Lower bone mass than C57BL/6
(
Kaye and Kusy, 1995). Low retinal ganglion
cell number (4/24) (
Williams et al, 1996).
Drugs
Susceptible to urethane-induced lung tumours (1/6) (
Falconer and Bloom, 1962). Sensitive to induction of pulmonary
tumours (1/6) but resistant to leukaemia and liver tumour induction by
DMBA given neonatally (6/6 and 5/6, respectively) (
Flaks,
1968). Susceptible to the induction of lung tumours by cyclopenta(cd)pyrene
(
Nesnow et al, 1994). Most benzo(a)pyrine-induced
lung tumours had K-ras oncogenes inherited from the A/J parent with mRNA
transcribed from the allele inherited from strain A/J being 5-20 times
more abundant than that from C3H in crosses involving strain C3H (
Chen et al, 1994) The A/J mouse lung can be used as a
model to study the effectiveness of new chemical intervention therapies
for controlling malignant tumor growth (
Belinsky
et al, 1993), and in the study of chemopreventive agents such as dietary
and green tea polyphenols (
Castonguay
and Packer, 1993, Katiyar et al, 1993),
isothiocyanates (AdamRodwell et al, 1993
, Hecht,
1995), vitamin E (Yano et al, 1994) and other substances (
Yun et al, 1995). No glycerol-associated effect on active
oxygen formation and thiobarbituric acid reactive substances was observed
in the lungs of A/J mice treated with 4-nitroquinoline 1-oxide, in contrast
with outbred ddY strain mice (
Yano et al, 1993,
1994).
Nicotine decreases shock avoidance learning in J substrain (7/9), but increases
it in He substrain (2/9) (Bovet et al., 1966.,
1966). Low ED50 to behavioural effects of nicotine (2/19). Resistant to
seizures induced by nicotine (2/19) (Marks
et al 1989) Susceptible to skin ulceration by DMBA (cf. 13/22) (Thomas et al., 1973., 1973). Not sensitive
to histamine (8/9) (Brown, 1965). Susceptible
to the teratogenic effect (cleft palate) of cortisone acetate (1/4) (Dostál
and Jel\'92; Kalter, 1965lter, 1965, Kalter
1981). There appears to be a threshold dose of cortisone needed to induce
cleft palate (Fawcett et al, 1996).
Sensitive to teratogenic effect (malformed ribs and vertebrae) of hypoxia
on ninth day of gestation (1/5) (Dagg, 1966).
Sensitive to X-irradiation (22/27 in He substrain, 20/27 in J substrain)
(Roderick, 1963), 9/10 in males, 8/10 in females
of J substrain (Storer, 1966). Highly susceptible
to endotoxin lipopolysaccharide (1/5) (Heppner
and Weiss, 1965). Resistant to hyperbaric oxygen (15/18 in J substrain,
12/18 in He substrain) (Hill et al., 1968.,
1968). Susceptible to pulmonary hyaline-membrane formation in 90% oxygen
(3/10) (Lieberman and Kellog, 1967).
Low LD50 to X-irradiation (7/9) (Yuhas
and Storer, 1969). Interstitial tumours of testis readily induced
with oestrogens (Heston, 1963). Sensitive to
chloroform toxicity (cf. 4/9) (Deringer
et al., 1953., 1953). Thalidomide increases congenital malformations
such as cleft lip and palate (Szabo and Steelman,
1967)..High bronchial reactivity (1/6) to methacholine and serotonin
(Konno et al 1993). Susceptible (1/8)
to daunomycin-induced nephorsis (Kimura et
al 1993). Resistant to hepatotoxic effects of cadmium (Shaikh et al, 1993). Airways hyperreactive to acetylcholine
(c.f. 3/7) (Zhang et al, 1995). Susceptible
(cf 5/8) to ozone-induced decreases of tracheal potential (Takahashi et al, 1995). Clonidene failed to produce an
aggressive behavioural response (cf 3/9) (Nikulina
and Klimek, 1993). A diet containing 15% dairy fat, 1% cholesterol
and 0.5% cholic acid caused a high incidence of cholesterol gallstones
(like SWR, C57L, contrast SM, AKR, DBA/2) (Faulkner
et al, 1995).
Immunology
Develops autoimmune phenomena, immunological deficits with ageing and autoimmunity
following neonatal thymectomy (
Yunis et al.,
1972., 1972). Low lymphocyte phytohaemagglutinin response (32/43)
(
Heiniger et al., 1975., 1975). Serum
antinuclear factor 11% (7/18) (
Barnes and
Tuffrey, 1967). 11% incidence of antinuclear antibody by 16 months
(1/17 in J substrain) (
Teague et al., 1972.,
1972). Good immune response to small doses of bovine gamma-globulin (cf.
4/8) (
Levine and Vaz, 1970). Poor immune
response to Cholera A and B antigens (7/9A, 6/8B) (
Cerny et al., 1971., 1971). Good immune response to ovomucoid
but poor response to bovine serum albumin (1/6) (
James
and Milne, 1972). Good immune response to DNP-keyhole limpet haemocyanin
(1/33 in J substrain, 3/11 in He substrain) (
Borel
and Kilham, 1974). Good immune response to GAT (random terpolymer
of Glu
60, Ala
30, Tyr
10) (1/10 in He substrain,
3/10 in J substrain) (
Dorf et al., 1974.,
1974). Poor primary haemagglutinin immune response to sheep erythrocytes
at 3 x 10
7 and 3 x 10
8 dose rates (6/6 and 5/6,
respectively), also poor haemolysin response at both doses (6/6) (
Ghaffar and James, 1973). High IgM antibody response to
sheep red blood cells compared with C57BL/10ScSn (
Vetvicka et al, 1993). Non-responder to synthetic polypeptide
Glu
57, Lys
38, m-Ala
5 (cf. 4/7) (
Pinchuck and Maurer, 1965). High antibody affinity to HSA
(1/9) (
Petty et al, 1972 , 1972). Erythrocytes
have a high agglutinability (cf. 14/25) (
Rubinstein
et al., 1974., 1974). Low immune response to ferritin in A-
Thy1.1
(16/16) (
Young et al., 1976., 1976).
Low responder to dextran (cf. 6/10) (
Blomberg
et al., 1972., 1972). Non-discrimination between `H' and `L' sheep
erythrocytes (cf. 6/18) (
McCarthy and Dutton,
1975). Susceptible (1/12) to experimental autoimmune orchitis induced
by two or three sc injections with viable syngeneic testicular germ cells
without any adjuvants (
Tokunaga et al 1993).
Resistant to ineduction of experimental allergic encephalomyelitis (10/10)
(
Lindsey, 1996). High immune response to ganglio-series
gangliosides (c.f. 2/10) Kawashima et al (
1992).
Interleukin-3 alone does not support hematopoetic colony formation of bone
marrow cells from these mice. Interleukin-3R alpha is not detectible on
the cell surface by antibody staining, though it is present inside the
cells (Ichihara et al, 1995, Leslie et al, 1996)). High immunological response to
Salmonella typhi porins (2/4) (Gonzales et al, 1995)
Infection
Resistant to infection by
Salmonella typhimurium strain C5 (6/7)
(
Plant and Glynn, 1974), (5/5) Robson and
Vas (
1972). This may be associated with
activation of complement (
Nakano et al, 1995).
100-fold more susceptible to
Listeria monocytogenes than C57BL/6
when measured by median lethal does (
Sadarangani
et al 1980). This seems to be associated with reduced levels of gamma
interferon and granulocyte-macrophage colony stimulating factor compared
with resistant C57BL/6 mice (
Iizawa et al,
1993). Susceptible to
Plasmodium berghei (3/8) (
Most et al., 1966., 1966). Highly susceptible to mammary
tumour virus, which is carried in an acute form in unfostered substrains
(
Murray and Little, 1967). High susceptibility
to BALB/Tennant leukaemia virus (2/12) (
Tennant,
1965). Susceptible to
Herpes simplex virus (9/11) (
Lopez,
1975). Resistant to oncogenic effects of polyoma virus given at birth
(
Law, 1966a). Susceptible to
Mycobacterium
marinum (1/9) but poor plateau harvest of M.
leprae 8 months
after infection (7/9) (
Shepard and Habas,
1967). Susceptible to infection by
Mycobacterium marinum
(2/6) (
Yamamoto et al 1991). Resistant
to mouse hepatitis virus type 3 infection (1/12 in J substrain and 2/12
in Orl substrain) though Ps substrain susceptible (
Le
Prevost et al., 1975., 1975). High mortality in a natural epizootic
of ectromelia (1/8) (
Briody, 1966). Resistant
to mouse hepatitis virus (
Bang and Warwick,
1960). Susceptible (1/10) to infection with
Ehrlichia risticii
(
Williams and Timoney, 1994). Resistant,
with low amylase response to the fungus
Paracoccidioides brasiliensis
(cf 6/12) (
Xidieh et al, 1994).
Encephalomyocarditis virus causes diabetes mellitus (cp. 7/14) (Boucher et al., 1975., 1975). Highly susceptible to infection
by measles virus (cf. 3/6) (Rager-Zisman
et al., 1976., 1976). Legionella pneumophila replicates within
and kills thioglycolate-elicited macrophages, in contrast with strain
BALB/c. This is associated with differences in availability of intracellular
iron (Gebran et al, 1994). Develop acute
pneumonia that resembles human Legionnaire's disease 24 to 48 hours after
intratracheal inoculation of Legionella pneumophila (Brieland et al, 1994). Susceptibility to most strains of
Legionella depends on the Lgn1 locus (Miyamoto
et al, 1996). Resistant to the lethal effects of murine hepatitis
virus strain 3 (contrast BALB/c), but resistance destroyed by methylprednisolone
(Fingerote et al, 1995). Highly susceptible
to infection with Candida albicans (1/6) (Ashman et al,1996)
Reproduction
Intermediate breeding performance (16/26), colony output 0.9 young per
female per week, litter size at weaning low at 4.4(21/25) (Festing, 1976a).
Intermediate breeding performance (6/8), litter size 4.9, sterility 11.5%(
Nagasawa et al., 1973., 1973). Low litter
size (5/6) and large proportion of infertile matings (5/6) (
Fernandes et al., 1973., 1973). Low litter size (5/6 and
4/6 in He substrain, J substrain) (
Verley
et al., 1967., 1967). Intermediate breeding performance (10/24) (
Hansen et al., 1973., 1973). High ratio of
females at birth (1/11) (
Cook and Vlcek, 1961).
dba/2
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15091 AK, hepatoma H6, round cell tumour C 1300 and spindle cell sarcoma
Sal (Kaliss, 1972). Injection of murine C-1300 neuroblastoma cells derived
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Iwakawa et al, 1994)
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INBRED STRAINS OF MICE
Updated 9 Apr. 1998
Michael FW
Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester,
UK
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