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Veterinary Physiology

Hiroetsu SUZUKI, DVM, PhD
Position : Professor
Lab. Location : Veterinary Physiology Laboratory, 5th Floor, Building D;
President’s Office, 1st floor, Building E
E-mail : hiroetsu(@mark)nvlu.ac.jp
researchmap : 1000192387
KAKEN Research Number : 50277662

Main Research Themes
Pathological and genetic analysis of spontaneous mutation

Research Keywords
Mutation, Disease Model, Renal Failure, Infertility, Epilepsy, Diabetes, Lethality, Dwarfism, Osteochondrodysplasia, Giantin, Astrin, Wwox, Phenotypic Analysis, Linkage Analysis

Research

　By making full use of veterinary methods, we conduct research based on the concept of clarifying the normal (physiological state) from the analysis of the abnormal (pathological state). In particular, we are using an original mutant rat strain to analyze its pathology, identify the causative gene, and evaluate its significance as a disease model. The main rat strains are listed below.

　We conduct research based on the concept of elucidating normal (physiological) states through the analysis of abnormalities (pathological states) using veterinary approaches. Specifically, we utilize original rat mutant strains to analyze pathological conditions, identify causative genes, and establish their significance as disease models. Recently, we have been analyzing the functions of identified causative genes at the cellular level using molecular biological methods. The main rat strains are listed below.

1. hypogonadism (HGN)：
A loss-of-function mutation in the microtubule-associated protein astrin, which is involved in spindle formation during the metaphase of somatic cell division, lead to testicular hypoplasia due to abnormal Sertoli cell division in males, early infertility due to ovarian hypoplasia in females, and progressive renal dysfunction due to renal hypoplasia in both sexes.
2. Lethal dwarfism with epilepsy (LDE)：
A loss-of-function mutation in Wwox, which was identified as an anti-tumor factor, causes developmental disorders in the nervous system, especially hypomyelination, resulting in epilepsy and developmental disorders. This serves as a model for childhood WOREE syndrome.
3. Osteochondrodysplasia (OCD)：
A loss-of-function mutation in giantin, which is involved in intracellular vesicle transport and primary cilia formation, results in lethal osteochondral dysplasia accompanied by systemic subcutaneous edema. Abnormal production and secretion of extracellular matrix is observed in chondrocytes.
4. Diabetes with enlarged kidney (DEK)：
Diabetes develops only in males, with affected individuals exhibiting marked enlargement of renal parenchyma. Unilateral nephrectomy immediately after onset prevents the development of diabetes, suggesting that the enlargement of renal parenchyma may trigger diabetes.
5. Other strains:：
dwarfism with thymic hypoplasia (PET), unilateral urogenital anomaly (UUA), etc.

Guidance Policy for Graduate Students

　In principle, research is conducted using one of the mutant strains. Because each strain has a different phenotype and requires different analysis methods, we use a variety of experimental techniques including histopathological morphology, genetic analysis, electrophysiology, biochemistry, molecular biology, and cell biology. To date, there had been two doctoral students at HGN, two at LDE, one at PET, one at UUA, and one at DEK, and they have greatly contributed to the analysis of each strain. For submitted papers, we aim not solely for veterinary journals but rather for specialized journals that align with the characteristics of each phenotype. After obtaining their doctorates, graduates have successfully pursued careers in diverse fields, including the Niigata University Kidney Research Center, the Institute of Environmental Toxicology, the Pharmaceuticals and Medical Devices Agency, university faculty positions, and small animal clinical practice. As I currently also serve as president, the associate professor of the Physiology Laboratory will provide direct guidance for those interested in advancing in this research, with regular meetings to ensure support. If you are interested, please feel free to come and hear an explanation.

Publications

HGN
1. Critical roles of Astrin in the mitosis of immature rat Sertoli cells.
Tochigi Y, Iwasaki Y, Sano M, Yasuda H, Katayama K, Suzuki H. (2017).
Biochem Biophys Res Commun, 13;486(4):958-964.
DOI: 10.1016/j.bbrc.2017.03.137.
2. Progression of renal fibrosis in congenital CKD model rats with reduced number of nephrons.
Yasuda H, Tochigi Y, Katayama K, Suzuki H. (2017). (Graduate student as first author)
Exp Toxicol Pathol, 14;69(5):245-258.
DOI: 10.1016/j.etp.2017.01.007
3. Renal Function and Hematology in Rats with Congenital Renal Hypoplasia.
Yasuda H, Amakasu K, Tochigi Y, Katayama K, Suzuki H. (2016). (Graduate student as first author)
Comp Med, 66(1):10-20
4. The microtubule-associated protein astrin transgenesis rescues spermatogenesis and renal function in hypogonadic (hgn/hgn) rats.
Katayama K, Yasuda H, Tochigi Y, Suzuki H. (2013).
Andrology, 1(2):301-7.
DOI: 10.1111/j.2047-2927.2012.00032.x
5. Reduced mitotic activity and increased apoptosis of fetal sertoli cells in rat hypogonadic (hgn/hgn) testes.
Yagi M, Takenaka M, Suzuki K, Suzuki H.(2007). (Graduate student as first author)
J Reprod Dev, 53(3):581-9
DOI: 10.1262/jrd.18128
6. Duplicated insertion mutation in the microtubule-associated protein Spag5 (astrin/MAP126) and defective proliferation of immatureSertoli cells in rat hypogonadic (hgn/hgn) testes.
Suzuki H, Yagi M, Suzuki K. (2006).
Reproduction, 132(1):79-93.
DOI: 10.1530/rep.1.01104
7. Apoptotic Sertoli cell death in hypogonadic (hgn/hgn) rat testes during early postnatal development.
Yagi M, Suzuki K, Suzuki H. (2006). (Graduate student as first author)
Asian J Androl, 8(5):535-41.
DOI: 10.1111/j.1745-7262.2006.00181.x
8. Age-related pathophysiological changes in rat oligomeganephronic hypoplastic kidney.
Suzuki H, Tokuriki T, Kamita H, Oota C, Takasu M, Saito K, Suzuki K. (2006).
Pediatr Nephrol, 21(5):637-42.
DOI: 10.1007/s00467-006-0089-3
9. Glomerular hyperfiltration and hypertrophy in the rat hypoplastic kidney as a model of oligomeganephronic disease.
Suzuki H, Tokuriki T, Saito K, Hishida A, Suzuki K. (2005).
Nephrol Dial Transplant, 20(7):1362-9.
DOI: 10.1093/ndt/gfh782
10. Dysplastic development of seminiferous tubules and interstitial tissue in rat hypogonadic (hgn/hgn) testes.
Suzuki H, Yagi M, Saito K, Suzuki K. (2004).
Biol Reprod, 71(1):104-16.
DOI: 10.1095/biolreprod.103.024604
LDE
11. Cellular Expression and Subcellular Localization of Wwox Protein During Testicular Development and Spermatogenesis in Rats.
Mahmud MAA, Noguchi M, Domon A, Tochigi Y, Katayama K, Suzuki H. (International graduate student as first authors)
J Histochem Cytochem, 69(4):257-270.
DOI: 10.1369/0022155421991629
12. Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development
Iacomino M, Baldassari S, Tochigi Y, Kośla K, Buffelli F, Torella A, Severino M, Paladini D, Mandarà L, Riva A, Scala M, Balagura G, Accogli A, Nigro V, Minetti C, Fulcheri E, Zara F, Bednarek AK, Striano P, Suzuki H, Salpietro V. (2020). (Collaborative research with University of London)
Front Neurosci, 11;14:644.
DOI: 10.3389/fnins.2020.00644
13. Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy
Tochigi Y, Takamatsu Y, Nakane J, Nakai R, Katayama K, Suzuki H. (2019).
Int J Mol Sci, 23;20(14):3596.
DOI: 10.3390/ijms20143596
14. A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy
Suzuki H, Katayama K, Takenaka M, Amakasu K, Saito K, Suzuki K. (2009).
Genes Brain Behav, 8(7):650-60.
DOI: 10.1111/j.1601-183X.2009.00502.x
15. Retarded differentiation of Leydig cells and increased apoptosis of germ cells in the initial round of spermatogenesis of rats with lethal dwarf and epilepsy (lde/lde) phenotypes
Takenaka M, Yagi M, Amakasu K, Suzuki K, Suzuki H. (2008). (Graduate student as first author)
J Androl, 29(6):669-78
DOI: 10.2164/jandrol.108.005066
OCD
16. Giantin is required for coordinated production of aggrecan, link protein and type XI collagen during chondrogenesis
Katayama K, Kuriki M, Kamiya T, Tochigi Y, Suzuki H. (2018).
Biochem Biophys Res Commun, 15;499(3):459-465.
DOI: <10.1016/j.bbrc.2018.03.163/td>
17. A role for the Golgi matrix protein giantin in ciliogenesis through control of the localization of dynein-2
Asante D, Maccarthy-Morrogh L, Townley AK, Weiss MA, Katayama K, Palmer KJ, Suzuki H, Westlake CJ, Stephens DJ. (2013). (Collaborative research with University of Bristol)
J Cell Sci, 15;126(Pt 22):5189-97.
DOI: 10.1242/jcs.131664
18. Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat
Katayama K, Sasaki T, Goto S, Ogasawara K, Maru H, Suzuki K, Suzuki H. (2011).
Bone, 49(5):1027-36.
DOI: 10.1016/j.bone.2011.08.001
DEK
19. Characterization of Enlarged Kidneys and Their Potential for Inducing Diabetes in DEK Rats
Domon A, Katayama K, Yamada T, Tochigi Y, Suzuki H. (2021). (Graduate student as first author)
Biology (Basel), 8;10(7):633.
DOI: 10.3390/biology10070633
20. Empagliflozin ameliorates symptoms of diabetes and renal tubular dysfunction in a rat model of diabetes with enlarged kidney (DEK)
Domon A, Katayama K, Sato T, Tochigi Y, Tazaki H, Suzuki H. (2021). (Graduate student as first author)
PLoS One, 4;16(5):e0251135.
DOI: 10.1371/journal.pone.0251135
21. Characterization of Novel Nonobese Type 2 Diabetes Rat Model with Enlarged Kidneys.
Domon A, Katayama K, Tochigi Y, Suzuki H. (2019). (Graduate student as first author)
J Diabetes Res, 31;2019:8153140.
DOI: 10.1155/2019/8153140
Other Strains
22. Age-related pathophysiological changes in rats with unilateral renal agenesis
Amakasu K, Suzuki K, Katayama K, Suzuki H. (2011). (Graduate student as first author)
J Vet Med Sci, 73(6):787-95.
DOI: 10.1292/jvms.10-0498
23. The unilateral urogenital anomalies (UUA) rat: a new mutant strain associated with unilateral renal agenesis, cryptorchidism, and malformations of reproductive organs restricted to the left side
Amakasu K, Suzuki K, Suzuki H. (2009). (Graduate student as first author)
Comp Med, 59(3):249-56.
24. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males
Chiba J, Suzuki H, Aoyama H, Katayama K, Suzuki K. (2011). (Graduate student as first author)
J Vet Med Sci, 73(4):495-9
DOI: 10.1292/jvms.10-0397
25. The petit rat (pet/pet), a new semilethal mutant dwarf rat with thymic and testicular anomalies
Chiba J, Suzuki K, Suzuki H. (2008). (Graduate student as first author)
Comp Med, 58(6):551-9.