DA

Inbr.F77 (Han 1989).

Colour: Agouti .

Genet. A, C, H.

Origin: Developed from stock of unstated origin by Dr. T.T. Odell, Jr. at Oak Ridge National Laboratory, Tennessee to F11, then by Dr. Darcy Wilson at the Wistar Institute, who named it DA because it expressed the d blood group allele of Joy Palm, and it is agouti in colour (Wilson 1965). Inbreeding was completed in about 1965. Although Palm and Black (1971) suggest it may be related to COP, there is no real evidence that this is the case.

Characteristics:

Lifespan and spontaneous disease

Urinary bladder tumours 54% in males and 14% in females, with a peak incidence at 25-30 months of age (Deerberg et al 1985). High incidence of hormone-dependent endometrial adenocarcinoma. A transplantable cell line (RUCA-I) derived from such a tumour in DA rats can produce these tumours in ectopic sites. The rate of proliferation is reduced by tamoxifen, and this cell line appears to be a suitable model for the study of molecular aspects of estrogen and tamoxifen-dependent gene expression. See also strain BDII/Han (Schutze et al, 1992). Urolithiasis found in 2/78 female rats at an average age of 118 days (Kunstyr et al 1982).

Biochemistry and physiology

Possible model for deficiency of debrisoquine hydroxylation due to a lack of Cyp2D1 activity, which is equivalent to human Cyp2D6 (Al-Dabbagh et al 1981), with the defect being due to a structurally altered db1 protein (Gonzalez et al 1987). At least one other isoform of P450 of the Cyp2C or Cyp3A families may also be missing. Although DA rats may be used as a preliminary screen to identify Cyp2D6 substrates, interspecies differences in metabolism means that this strain could not be used to provide quantitative information regarding the contribution of Cyp2D6 to an oxidation in humans (Barham et al, 1994)

Defective bile acid transport found in females, which may be related to deficient debrisoquine hydroxylation (Reichen et al 1986). Hackbarth et al (1981) have described the glomerular filtration rate and renal plasma flow in DA and other strains, and haematological parameters and their relation to diet have been described by Hackbarth et al (1983). In studies of food intake and body weight gain, DA rats ingested mainly proteins and fats, in contrast with outbred Wistar rats which ate about equal quantities of fat, protein and carbohydrate (Larueachagiotis et al, 1994).

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Reproduction

Short gestation period (1/8) (Peters 1986).

Drugs and chemicals

Susceptible (1/7) to the development of 4-nitroquinoline 1-oxide induced squamous cell carcinomas of the tongue, with high proliferative response of the tongue epithelium (contrast WF) (Kitano et al, 1992).

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Immunology

Susceptible to the induction of autoimmune thyroiditis (Rose 1975). Develop severe collagen-induced arthritis following immunisation with bovine, chick or rat type II collagens. This is exacerbated by infection with rat cytomegalovirus. However, the congenic strain DA.1N(BN) is much more resistant (Griffiths et al, 1994). Develops arthritis after injection of Freund's incomplete adjuvent alone (oil-induced arthritis, OIA). This is a self-limiting acute disease whereas collagen-induced arthritis follows a chronic course (Holmdahl and Kvick, 1992, 1994). DA is sensitive whereas LEW are relatively resistant (Holmdahl et al, 1992). A strong local expression of TNF-alpha, induced by arthritogenic stimuli may be important for the induction of arthritis (Mussener et al, 1995). Susceptible to the development of experimental allergic encephalomyelitis upon treatment with a myelin basic protein-specific T cell line derived from an F1 hybrid between resistant AO and susceptible DA strain rats (Mostaricastrojkovic et al, 1992). Although DA and LEW are both highly susceptible to the development of EAE, there are marked differences in the array of myelin epitopes capable of inducing the disease as well as MHC restriction of these epitopes between the two strains (Stepaniak et al, 1995).

Resistant to the development of experimental glomerulonephritis following injection of nephritogenic antigen from bovine renal basement membrane (10/10) (Naito et al, 1991). Met-enkephalin increased H₂O₂ production by macrophages (contrast AO) (Radulovic et al, 1995).

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Infection

Infection with Hymenolepsis diminuata cysticercoids results in significant mastocytosis six weeks post infection and low persistance of worms, in contrast with F344, where there was no worm loss and no mastocytosis (Ishih, 1992, 1994).

Dahl R and Dahl S (Mollegard)

Origin: see SR and SS and also DSS/1 to DSS/3

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Al-Dabbagh S. G., Idle J. R., and Smith R. L. (1981) Animal modelling of human polymorphic drug oxidation- the metabolism of debrisoquine and phenacetin in rat inbred strains. J. Pharm. Pharmacol. 33, 161-164.

Deerberg F., Rehm S., and Jostmeyer H. H. (1985) Spontaneous urinary bladder tumors in DA/Han rats: A feasible model of human bladder cancer. J. Natl. Cancer Inst. 75, 1113-1121.

Griffiths M. M., Sawitzke A. D., Harper D. S., McCall S., Reese V. R., and Cannon G. W. (1994) Exacerbation of collagen-induced arthritis in rats by rat cytomegalovirus is antigen-specific. Autoimmunity 18, 177-187.

Hackbarth H., Baunack E., and Winn M. (1981) Strain differences in kidney function of inbred rats: 1. Glomerular filtration rate and renal plasma flow. Lab. Anim. 15, 125-128.

Hackbarth H., Burow K., and Schimansky G. (1983) Strain differences in inbred rats: Influence of strain and diet on haematological traits. Lab. Anim. 17, 7-12.

Holmdahl R. and Kvick C. (1992) Vaccination and genetic experiments demonstrate that adjuvant-oil- induced arthritis and homologous type-II collagen-induced arthritis in the same rat strain are different diseases. Clin. Exp. Immunol. 88, 96-100.

Ishih A. (1992) Mucosal mast-cell response to hymenolepis-diminuta infection in different rat strains. International Journal for Parasitology 22, 1033-1035.

Kitano M., Hatano H., and Shisa H. (1992) Strain difference of susceptibility to 4-nitroquinoline 1-oxide- induced tongue carcinoma in rats. Jpn. J. Cancer Res. 83, 843-850.

Kunstyr I., Naumann S., and Werner J. (1982) Urolithiasis in female inbred SPF rats. Possible predisposition of DA and ACI strains. Z. Versuchstierk. 24, 214-218.

Larueachagiotis C., Goubern M., Laury M. C., and Louissylvestre J. (1994) Energy-balance in an inbred strain of rats - comparison with the Wistar strain. Physiol. Behav. 55, 483-487.

Mussener A., Klareskog L., Lorentzen J. C., and Kleinau S. (1995) Tnf-alpha dominates cytokine messenger-RNA expression in lymphoid- tissues of rats developing collagen-induced and oil-induced arthritis. Scand.J. Immunol. 42, 128-134.

Naito I., Kagawa M., Sado Y., and Okigaki T. (1991) Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis - presence of a broad- spectrum of the susceptibility. International Journal of Immunopathology and Pharmacology 4, 145-154.

Palm J. and Black G. (1971) Interrelationships of inbred rat strains with respect to Ag-B and non-Ag-B antigens. Transplant. 11, 184-189.

Peters A. (1986) Length of gestation period in eight inbred strains and three outbred stocks of rats. Animal Technology 37, 109-112.

Reichen J., Krahenbuhl S., Kupfer A., Sagresser H., and Karlaganis G. (1986) Defective bile acid transport in an animal model of defective debrisoquine hydroxylation. Biochem. Pharmacol. 35, 753-759.

Rose N. R. (1975) Differing responses of inbred rat strains in experimental autoimmune thyroiditis. Cell. Immunol. 18, 360-364.

Schutze N., Kraft V., Deerberg F., Winking H., Meitinger D., Ebert K., Knuppen R., and Vollmer G. (1992) Functions of estrogens and antiestrogens in the rat endometrial adenocarcinoma cell-lines RUCA-I and RUCA-II. Int. J. Cancer 52, 941-949.

Stepaniak J. A., Gould K. E., Sun D. M., and Swanborg R. H. (1995) A comparative-study of experimental autoimmune encephalomyelitis in Lewis and DA rats. J. Immunol. 155, 2762-2769.

Wilson D. D. (1965) Quantitative studies on the behavior of sensitized lymphocytes in vitro. J. Exp. Med. 122, 143-166.

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INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK