Abstract
Hydrocephalus is a significant clinical condition in humans and is known to be a multifactorial neurologic disorder. It has been thought that genetic factors are closely involved in the etiology of congenital hydrocephalus, but further investigation is required to elucidate the genetic architecture of hydrocephalus. By analyzing breeding records of a panel of inter-subspecific consomic mouse strains, we found that consomic strains with MSM/Ms (MSM) chromosomes 4, 5, 7, 11, 15, and 17 showed a significantly higher incidence of hydrocephalus, whereas both parental strains, MSM and C57BL/6J (B6), rarely showed this abnormality. Further analysis of the consomic Chr 17 strain revealed that apparently normal individuals of this strain also exhibited increased brain ventricle size compared to B6 and had larger individual variation of ventricle size within the strain. Thus, we concluded that hydrocephalus is an extreme phenotype of individual ventricle size variation. We then established and analyzed several subconsomic strains of Chr 17 to identify genetic factors related to hydrocephalus-like phenotype and successfully mapped one genetic locus around the proximal region of Chr 17.
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Acknowledgments
The authors thank M. Arii, K. Takahashi, M. Nakajima, and D. Takahashi for rearing the mice and recording the information on consomic mouse strains; N. Hoshino for histologic analysis; and H. Yonekawa and A. Mita for establishing the consomic strains. This study was supported by the Japan Society for the Promotion of Science (A.T.), KAKENHI (Grant-in-Aid for Scientific Research) on Priority Areas “Comparative Genomics” from the Ministry of Education, Culture, Sports, Science and Technology (T.K. and T.S.), and the-Bio-diversity Research Project of Transdisciplinary Research Integration Center, Research Organization of Information and Systems (T.K. and T.S.). This study is contribution number 2510 from the NIG.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00335-008-9126-9
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Takahashi, A., Shiroishi, T. & Koide, T. Multigenic factors associated with a hydrocephalus-like phenotype found in inter-subspecific consomic mouse strains. Mamm Genome 19, 333–338 (2008). https://doi.org/10.1007/s00335-008-9112-2
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DOI: https://doi.org/10.1007/s00335-008-9112-2