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Genetic Dissection of Trabecular Bone Structure with Mouse Intersubspecific Consomic Strains
Taro Kataoka1,2, Masaru Tamura1,3, Akiteru Maeno1
1Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
G3 (Bethesda, Md.)
|September 1, 2017
Summary
Genetic factors significantly influence trabecular bone structure and fragility. Researchers identified four novel quantitative trait loci (Tbsq1-4) on mouse chromosome 15, revealing complex genetic regulation of bone strength.
Area of Science:
- Genetics
- Bone Biology
- Comparative Genomics
Background:
- Trabecular bone structure is critical for bone strength.
- The genetic basis for trabecular bone structure regulation remains largely unknown.
- Significant differences in trabecular bone fragility exist between mouse strains C57BL/6J and MSM/Ms.
Purpose of the Study:
- To identify genetic factors regulating trabecular bone structure.
- To pinpoint specific chromosomal regions and genes contributing to bone fragility differences.
- To understand the genetic architecture of trabecular bone integrity.
Main Methods:
- Comparative phenotyping of C57BL/6J and MSM/Ms mouse strains using X-ray micro-CT.
- Utilizing consomic mouse strains for systematic chromosome substitution analysis.
- Fine-mapping quantitative trait loci (QTL) on chromosome 15 using subconsomic strains.
Main Results:
- The MSM/Ms mouse strain exhibits more fragile trabecular bone than C57BL/6J.
- Consomic strain B6-Chr15MSM showed significantly altered bone structure parameters, indicating chromosome 15's role.
- Four novel QTLs (Tbsq1-4) associated with trabecular bone structure were mapped to mouse chromosome 15.
Conclusions:
- Trabecular bone structure is regulated by a complex interplay of multiple genes.
- Mouse chromosome 15 harbors key genetic determinants (Tbsq1-4) influencing bone fragility.
- Further investigation of Tbsq4, syntenic to human chromosome 12q12-13.3, may elucidate human bone formation genetics.
