(Hypertension. 2001;38:e9.)
© 2001 American Heart Association, Inc.
Letters to the Editor |
Letters to the Editor
Mislabelling of Donryu Rats
Department of Physiology, University of Melbourne, Victoria, Australia
Department of Internal Medicine, TEPCO Hospital, Tokyo, Japan
To the Editor:
Between 1992 and 2000, 21 papers1–21were published that used rats from inbred colonies in Melbourne and Tokyo that were believed to be of the Donryu (DRY) strain. These rats were thought to have been the same strain as DRY used by Dr Tanase in early breeding experiments in relation to blood pressure in spontaneously hypertensive rats(SHR).22, 23The original DRY strain had been held at the Sankyo Co, Ltd, in Japan. At sometime before 1991, however, it appears that in the company’s laboratories there had been an unrecognised substitution of Fisher344 (F344) for DRY (see below) and that authentic DRY were culled and no longer exist.
In 1991, the company supplied 5 brother-sister breeding pairs to the Melbourne Biological Research Facility at the Austin Hospital. Accompanying documentation attributed specific genetic biochemical profiles of the DRY strain to these animals and differentiated them from the F344, BUF (Buffalo), and LEW (Lewis) strains. A separate colony was also established in Tokyo in the same manner.
The subsequent generations of these animals were used predominantly in cross-breeding studies of blood pressure, cardiac size, and intracellular calcium. These studies included genome-wide mapping in which the purported Dry strain from the Melbourne colony was genotyped for polymorphic markers. These data were subsequently made available on the Internet(www.genome.wi.mit.edu/rat/public/).
Recently, Dr Tanase indicated that the animals supplied to Melbourne and Tokyo that had been labeled as DRY were instead likely to be F344 rats. The company believed that before transfer to Melbourne and Tokyo, the labeling of authentic DRY animals and F344 had been unknowingly and accidentally swapped, and the authentic Dry were culled as supposed F344 in excess to needs.
These revelations prompted a comparison of the public polymorphic markers for the purported DRY (from Melbourne) and the F344, which revealed a genotypic difference of only 7%. Further biochemical polymorphic analysis revealed no differences between the profiles of the purported DRY from Melbourne Andre ference F344. Other studies in Japan by Dr Tanase confirmed that the polymorphism profiles of 43 markers from chromosomes 1, 2, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 18, 19, 20, and X were completely consistent between the purported Donryu animals from Tokyo and known authentic F344 rats from Sankyo.
In addition, the DNA polymorphic profile of a previous cross derived from SHR and authentic DRY animals was compared against the profile of the purported DRY from Tokyo. Of the 43 markers tested, the comparisons were informative for 17 loci, for which the cross (derived from authentic DRY) and the purported DRY animals were identical at 7 and nonidentical at 10.
Therefore, based on the available evidence that the purported DRY showed only minor differences from F344 and significant differences from authentic DRY, we conclude that the animals described as DRY in the listed publications1–21were in fact inbred F344. In itself, this does not have implications for the results of the individual studies. The purported DRY were never intended tore present genetically appropriate controls for any strain, in particular SHR.Instead, they were intended simply as inbred normotensive controls, unrelated to SHR and used to maximize the informativeness of the linkage analyses. Infant, it is fortuitous that the control strain for crossbreeding studies of cardiac size should transpire to be the F344, which has one of the smallest hearts among normotensive rats.24
All subsequent publications that refer to these animals will use their correct designation of F344.
References
1. Harrap SB, Mitchell GA, Norman TL. Is cardiovascular hypertrophy in young SHR the result of a recessive gene? In: Sassard J, ed. Genetic Hypertension. Paris, France:Colloque INSERM/John Libbey Eurotext Ltd; 1992:341–343.
2. Jones EF, Harrap SB, Calafiore P, Tonkin AM. Development and validation of echocardiographic methods for estimating left ventricular mass. Clin Exp Pharm Physiol. 1992;19:361–364.
3. Campbell DJ, Duncan A-M, Kladis A, Harrap SB. Increased levels of bradykinin and its metabolites in tissues of young spontaneously hypertensive rats. J Hypertens. 1995;13:739–746.
4. Campbell DJ, Duncan A-M, Kladis A, Harrap SB. Angiotensin peptides in spontaneously hypertensive and normotensive Donryu rats. Hypertension. 1995;25:928–934.
5. Campbell DJ, Duncan A-M, Kladis A, Harrap SB. Converting enzyme inhibitor treatment and its withdrawal in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1995;26:426–436.
6. Kapuscinski M, Charchar F, Innes B, Mitchell GA, Norman TL, Harrap SB. Nerve growth factor gene and hypertension in spontaneously hypertensive rats. J Hypertens. 1996;14:191–197.
7. Kapuscinski MK, Nemoto K, Ueyama T, Charchar F, Kageyama H, Fukumachi K, Sekimoto M, Senba E, Tomita T, Tomita I, Harrap SB. Low affinity nerve growth factor receptor gene co-segregates with decreased body weight and increased left ventricular weight in spontaneously hypertensive rats. Clin Exp Pharm Physiol. 1996;23:614–616.
8. Harris EL, Grigor MR, Innes BA, Harrap SB, Koike G, Jacob HJ. Strain-specific deletions in exon 10 of rat K-kininogen and1-kininogen genes allow mapping of both genes to rat chromosome11. Mammalian Genome. 1997;8:791–792.
9. Naitoh M. Burrell LM. Risvanis J. Aldred KL. Rockell MD. Johnston CI. Phillips PA. Modulation of genetic hypertension by short-term AVP V1A or V2receptor antagonism in young SHR. Am J Physiol. 1997;272:F229–F234.
10. Harrap SB, Jones EF. Cardiovascular hypertrophy does not predispose genetic hypertension. Clin Exp Hypertens. 1997;19:531–541.
11. Innes BA, McLauglin MG, Kapuscinski MK, Jacob HJ, Harrap SB. Independent genetic susceptibility to cardiac hypertrophy ininherited hypertension. Hypertension. 1998;31:741–746.
12. Charchar FJ, Kapuscinscki M, Harrap SB. The nerve growth factor gene locus explains elevated nerve growth factor mRNA in young spontaneously hypertensive rats. Hypertension. 1998;32:705–709.
13. Stoll M, Kwitek-Black AE, Cowley AWJr, Harris EL, Harrap SB, Krieger JE, Printz MP, Provoost AP, Sassard J, Jacob HJ. New target regions for human hypertension via comparative genomics. Genome Res. 2000;10:473–482.
14. Aldred KL. Harris PJ. Eitle E. Increased proximal tubule NHE-3 andH+-ATPase activities in spontaneously hypertensive rats. J Hypertens. 2000;18:623–628.
15. Ohno Y, Suzuki H, Matsuo K, Tanase H, Takano T, Saruta T. Augmented Ca2+ mobilization is a hypertensive trait discriminated from a "major gene" in back cross analysis between SHR and Donryu rats. Clin Exp Pharmacol Physiol. Suppl 1995;1:S220–S222.
16. Ohno Y, Matsuo K, Suzuki H, Tanase H, Serikawa T, Takano T, Saruta T. Genetic linkage of the sarco(endo)plasmic reticulum Ca2+ -dependent ATPase II gene to intracellular Ca2+ concentration in the spontaneously hypertensive rat. Biochem Biophys Res Commun. 1996;227:789–793.
17. Ohno Y, Matsuo K, Suzuki H, Tanase H, Ikeshima H, Takano T, Saruta T. Genotypes of sarco(endo)plasmic reticulum Ca2+ -dependent ATPase II gene in substrains of spontaneously hypertensive rats. J Hypertens. 1996;14:287–291.
18. Nabika T, Ito T, Kitada K, Serikawa T, Mashimo T, Soubrier F, Julier C, Ohno Y, Saruta T, Tanase H, Masuda J, Yamori Y, Nara Y. Comparative mapping of novel simple sequence repeat markers in a hypertension-related region on rat chromosome 1. Mamm Genome. 1997;8:215–217.
19. Ohno Y, Matsuo K, Suzuki H, Tanase H, Takano T, Saruta T. Increased intracellular Ca2+ is not coinherited with an inferred major gene locus for hypertension (ht) in the spontaneously hypertensive rat. Am J Hypertens. 1997;10:282–288.
20. Ohno Y, Tanase H, Nabika T, Otsuka K, Sasaki T, Suzawa T, Morii T, Yamori Y, Saruta T. Selective genotyping with epistasis can be utilized for a major quantitative trait locus mapping in hypertension in rats. Genetics. 2000;155:785–792.
21. Mashimo T, Nabika T, Kitada K, Serikawa T, Matsumoto C, Ikeda K, Nara Y, Masuda J, Yamori Y, Ohno Y, Saruta T. Mapping of four simple sequence repeat (SSR) markers on rat chromosome 4. Hypertens Res. 2000;23:47–50.
22. Tanase H, Suzuki Y, Ooshima A, Yamori Y, Okamoto K. Genetic analysis of blood pressure in spontaneously hypertensive rats. Jap Circ J. 1970;34:1197–1212.
23. Tanase H. Genetic control of blood pressure in spontaneously hypertensive rats (SHR). Exp Animals. 1979;34:1197–1212.
24. Tanase H. Yamori Y. Hansen CT. Lovenberg W. Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats. Hypertension. 1982;4:864–872.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||