Genetic Dissection of Trabecular Bone Structure with Mouse Intersubspecific Consomic Strains
| Autor: | Shigeharu Wakana, Toshihiko Shiroishi, Taro Kataoka, Akiteru Maeno, Masaru Tamura |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genotype QTL Quantitative Trait Loci MSM/Ms Consomic Strain Mice Inbred Strains Single-nucleotide polymorphism Investigations QH426-470 Quantitative trait locus Biology consomic mouse strains Mice 03 medical and health sciences Chromosome 15 trabecular bone structure C57BL/6J Genetics Animals Humans Molecular Biology Genetics (clinical) Synteny Chromosomes Human Pair 15 Chromosome X-Ray Microtomography Phenotype Trabecular bone 030104 developmental biology Cancellous Bone |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 7, Iss 10, Pp 3449-3457 (2017) G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| DOI: | 10.1534/g3.117.300213 |
| Popis: | Trabecular bone structure has an important influence on bone strength, but little is known about its genetic regulation. To elucidate the genetic factor(s) regulating trabecular bone structure, we compared the trabecular bone structures of two genetically remote mouse strains, C57BL/6J and Japanese wild mouse-derived MSM/Ms. Phenotyping by X-ray micro-CT revealed that MSM/Ms has structurally more fragile trabecular bone than C57BL/6J. Toward identification of genetic determinants for the difference in fragility of trabecular bone between the two mouse strains, we employed phenotype screening of consomic mouse strains in which each C57BL/6J chromosome is substituted by its counterpart from MSM/Ms. The results showed that many chromosomes affect trabecular bone structure, and that the consomic strain B6-Chr15MSM, carrying MSM/Ms-derived chromosome 15 (Chr15), has the lowest values for the parameters BV/TV, Tb.N, and Conn.D, and the highest values for the parameters Tb.Sp and SMI. Subsequent phenotyping of subconsomic strains for Chr15 mapped four novel trabecular bone structure-related QTL (Tbsq1-4) on mouse Chr15. These results collectively indicate that genetic regulation of trabecular bone structure is highly complex, and that even in the single Chr15, the combined action of the four Tbsqs controls the fragility of trabecular bone. Given that Tbsq4 is syntenic to human Chr 12q12-13.3, where several bone-related SNPs are assigned, further study of Tbsq4 should facilitate our understanding of the genetic regulation of bone formation in humans. |
| Databáze: | OpenAIRE |
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