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Open Access Phenotypic Characterization of the Komeda Miniature Rat Ishikawa, an Animal Model of Dwarfism Caused by a Mutation in Prkg2

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Abstract:

The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BN×KMI-mri/mri)F1×KMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII.

Document Type: Research Article

Affiliations: 1: Division of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University, Saitama, Japan 2: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan; Clinical Genome Informatics Center, Kobe University Graduate School of Medicine, Kobe, Japan 3: Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan 4: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan 5: Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco, Kanagawa, Japan 6: Research Administration, Drug Research Division, Dainippon Sumitomo Pharma, Osaka, Japan 7: Division of Laboratory Animal Science, Animal Research Center, Tokyo Medical University, Tokyo, Japan

Publication date: December 1, 2008

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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