OMIA:001160-9986 : Hyperlipidaemia in Oryctolagus cuniculus (rabbit)

In other species: chicken , dog , ass (donkey) , horse , pig , Japanese quail

Categories: Homeostasis / metabolism phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 143890 (trait) , 606945 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1986

Cross-species summary: see also OMIA:000499 : Hypercholesterolaemia

Species-specific name: Watanabe heritable hyperlipidemia

Species-specific symbol: WHHL

History: This strain of rabbit was first described by Watanabe (1980), who developed an inbred line homozygous for an autosomal recessive mutant first recognised in 1973. Named as the Watanabe Heritable HyperLipidemia (WHHL) strain in this 1980 paper, this strain was characterised by the author as having "abnormally increased serum levels of cholesterol (S-Ch) and triglyceride (S-TG) at various ages, increased approximately 8- to 14-fold in comparison with control levels in normal Japanese white rabbits".

Inheritance: The hyperlipidaemia is inherited as an autosomal recessive.

Molecular basis: Using the candidate gene strategy (based on the characteristic hypercholesterolemia due to deficiency of LDL receptors), Yamamoto et al. (1986) compared the cDNA sequence of the LDL receptor in WHHL and normal rabbits, and discovered the causal mutation to be "an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
LDLR low density lipoprotein receptor Oryctolagus cuniculus NW_026259267.1 (1263395..1276393) LDLR Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
449 Hyperlipidaemia LDLR deletion, small (<=20) Naturally occurring variant "an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor" 1986 3010466

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2013). OMIA:001160-9986: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2020 Poznyak, A.V., Silaeva, Y.Y., Orekhov, A.N., Deykin, A.V. :
Animal models of human atherosclerosis: current progress. Braz J Med Biol Res 53:e9557, 2020. Pubmed reference: 32428130. DOI: 10.1590/1414-431x20209557.
2018 Hara, T., Tsukada, N., Okano, M., Ishida, T., Hirata, K.I., Shiomi, M. :
Progression of calcific aortic valve sclerosis in WHHLMI rabbits. Atherosclerosis 273:8-14, 2018. Pubmed reference: 29654986. DOI: 10.1016/j.atherosclerosis.2018.03.044.
2016 Baumgartner, C., Brandl, J., Münch, G., Ungerer, M. :
Rabbit models to study atherosclerosis and its complications - Transgenic vascular protein expression in vivo. Prog Biophys Mol Biol 121:131-41, 2016. Pubmed reference: 27261072. DOI: 10.1016/j.pbiomolbio.2016.05.001.
2013 Shiomi, M., Koike, T., Ito, T. :
Contribution of the WHHL rabbit, an animal model of familial hypercholesterolemia, to elucidation of the anti-atherosclerotic effects of statins. Atherosclerosis 231:39-47, 2013. Pubmed reference: 24125408. DOI: 10.1016/j.atherosclerosis.2013.08.030.
2012 [No authors listed] :
The tale of the Watanabe rabbit. Lab Anim (NY) 41:277, 2012. Pubmed reference: 22992501. DOI: 10.1038/laban1012-277.
2011 Kobayashi, T., Ito, T., Shiomi, M. :
Roles of the WHHL rabbit in translational research on hypercholesterolemia and cardiovascular diseases. J Biomed Biotechnol 2011:406473, 2011. Pubmed reference: 21541231. DOI: 10.1155/2011/406473.
2009 Shiomi, M., Ito, T. :
The Watanabe heritable hyperlipidemic (WHHL) rabbit, its characteristics and history of development: a tribute to the late Dr. Yoshio Watanabe. Atherosclerosis 207:1-7, 2009. Pubmed reference: 19389675. DOI: 10.1016/j.atherosclerosis.2009.03.024.
2008 Imanishi, T., Ikejima, H., Tsujioka, A., Kuroi, A., Kobayashi, K., Shiomi, M., Muragaki, Y., Mochizuki, S., Goto, M., Yoshida, K., Akasaka, T. :
Combined effects of an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and angiotensin II receptor antagonist on nitric oxide bioavailability and atherosclerotic change in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits. Hypertens Res 31:1199-208, 2008. Pubmed reference: 18716369. DOI: 10.1291/hypres.31.1199.
2004 Shiomi, M., Ito, T., Yamada, S., Kawashima, S., Fan, J. :
Correlation of vulnerable coronary plaques to sudden cardiac events. Lessons from a myocardial infarction-prone animal model (the WHHLMI rabbit). J Atheroscler Thromb 11:184-9, 2004. Pubmed reference: 15356377.
2003 Suzuki, H., Kobayashi, H., Sato, F., Yonemitsu, Y., Nakashima, Y., Sueishi, K. :
Plaque-stabilizing effect of pitavastatin in Watanabe heritable hyperlipidemic (WHHL) rabbits Journal of Atherosclerosis & Thrombosis 10:109-16, 2003.
2002 Murakami, S., Kondo, Y., Sakurai, T., Kitajima, H., Nagate, T. :
Taurine suppresses development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits Atherosclerosis 163:79-87, 2002. Pubmed reference: 12048124.
Sun, H., Usui, S., Shiomi, M., Watanabe, T., Fan, J. :
A rapid PCR method of genotyping LDL receptor mutations in WHHL rabbits. J Atheroscler Thromb 9:145-8, 2002. Pubmed reference: 12226556.
1998 Aliev, G., Burnstock, G. :
Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis. Histol Histopathol 13:797-817, 1998. Pubmed reference: 9690137.
1997 Coats, W.D., Whittaker, P., Cheung, D.T., Currier, J.W., Han, B., Faxon, D.P. :
Collagen content is significantly lower in restenotic versus nonrestenotic vessels after balloon angioplasty in the atherosclerotic rabbit model Circulation 95:1293-1300, 1997. Pubmed reference: 9054862.
Nordestgaard, B.G., Agerholm-Larsen, B., Mortensen, A., Hansen, B.F., Hansen, J.F., Ibsen, P., Kjeldsen, K. :
Intermediate density lipoprotein cholesterol as the best lipoprotein predictor of atherosclerosis severity in the watanabe heritable hyperlipidemic rabbit 132:119-122, 1997. Pubmed reference: 9247367.
1996 Eguchi, S., Rozga, J., Lebow, L.T., Chen, S.C., Wang, C.C., Rosenthal, R., Fogli, L., Hewitt, W.R., Middleton, Y., Demetriou, A.A. :
Treatment of hypercholesterolemia in the watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration stimulus Transplantation 62:588-593, 1996. Pubmed reference: 8830820.
Kanazawa, K., Kawashima, S., Mikami, S., Miwa, Y., Hirata, K., Suematsu, M., Hayashi, Y., Itoh, H., Yokoyama, M. :
Endothelial constitutive nitric oxide synthase protein and mRNA increased in rabbit atherosclerotic aorta despite impaired endothelium-dependent vascular relaxation American Journal of Pathology 148:1949-1956, 1996. Pubmed reference: 8669480.
Mortensen, A., Frandsen, H. :
Reproductive performance and changes in blood lipids in breeding females and in growing watanabe heritable hyperlipidaemic and new zealand white rabbits Laboratory Animals 30:252-259, 1996. Pubmed reference: 8843050.
Yuan, C., Skinner, M.P., Kaneko, E., Mitsumori, L.M., Hayes, C.E., Raines, E.W., Nelson, J.A., Ross, R. :
Magnetic resonance imaging to study lesions of atherosclerosis in the hyperlipidemic rabbit aorta Magnetic Resonance Imaging 14:93-102, 1996. Pubmed reference: 8656993.
1995 Chakrabarti, M., Cheng, K.T., Spicer, K.M., Kirsch, W.M., Fowler, S.D., Kelln, W., Griende, S., Nehlsencannarella, S., Willerson, R., Spicer, S.S., Koch, T. :
Biodistribution and radioimmunopharmacokinetics of I-131-AMA monoclonal antibody in atherosclerotic rabbits Nuclear Medicine & Biology 22:693-697, 1995.
Simonsen, K., Horn, T., Mortensen, A., Hansen, B.F., Hansen, J.F. :
Liver fibrosis in heterozygous WHHL rabbits fed cholesterol and fats; A new animal model International Hepatology Communications 3:310-315, 1995.
1991 Havel, R.J., Shames, D.M. :
Kinetic studies of the origin of apolipoprotein (apo) B-100 in low density lipoproteins of normal and Watanabe heritable hyperlipidemic (WHHL) rabbits. Adv Exp Med Biol 285:245-55, 1991. Pubmed reference: 1858553.
1990 Buja, L.M., Clubb, F.J., Bilheimer, D.W., Willerson, J.T. :
Pathobiology of human familial hypercholesterolaemia and a related animal model, the Watanabe heritable hyperlipidaemic rabbit. Eur Heart J 11 Suppl E:41-52, 1990. Pubmed reference: 2226533.
1989 Havel, R.J., Yamada, N., Shames, D.M. :
Watanabe heritable hyperlipidemic rabbit. Animal model for familial hypercholesterolemia. Arteriosclerosis 9:I33-8, 1989. Pubmed reference: 2643428.
Komiyama, Y., Masuda, M., Murakami, T., Nishikado, H., Egawa, H., Nishimura, T., Morii, S., Murata, K. :
Accumulation of I-125-Factor-XI in Atheroma of Rabbit with Hereditary Hyperlipidemia (Whhl-Rabbit) Thrombosis Research 56:49-58, 1989. Pubmed reference: 2595673.
1986 Yamamoto, T., Bishop, R.W., Brown, M.S., Goldstein, J.L., Russell, D.W. :
Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit. Science 232:1230-7, 1986. Pubmed reference: 3010466.
1984 Kawamata, J. :
[Experimental animal information file: WHHL (Watanabe heritable hyperlipidemic rabbit)]. Gan To Kagaku Ryoho 11:1895-7, 1984. Pubmed reference: 6476847.
1981 Kita, T., Brown, M.S., Watanabe, Y., Goldstein, J.L. :
Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. Proc Natl Acad Sci U S A 78:2268-72, 1981. Pubmed reference: 6264472.
Shimada, Y., Tanzawa, K., Kuroda, M., Tsujita, Y., Arai, M., Watanabe, Y. :
Biochemical characterization of skin fibroblasts derived from WHHL-rabbit, a notable animal model for familial hypercholesterolemia. Eur J Biochem 118:557-64, 1981. Pubmed reference: 6271553.
Watanabe, Y., Ito, T., Saeki, M., Kuroda, M., Tanzawa, K., Mochizuki, M., Tsujita, Y., Arai, M. :
Hypolipidemic effects of CS-500 (ML-236B) in WHHL-rabbit, a heritable animal model for hyperlipidemia. Atherosclerosis 38:27-31, 1981. Pubmed reference: 7470202.
1980 Tanzawa, K., Shimada, Y., Kuroda, M., Tsujita, Y., Arai, M., Watanabe, H. :
WHHL-rabbit: a low density lipoprotein receptor-deficient animal model for familial hypercholesterolemia. FEBS Lett 118:81-4, 1980. Pubmed reference: 7409195.
Watanabe, Y. :
Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). Atherosclerosis 36:261-8, 1980. Pubmed reference: 7406953.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 17 May 2013