Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes.

Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Research Abstract Details 

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Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Abstract Text:

Wesley G Beamer,Kathryn L Shultz,Cheryl L Ackert-Bicknell,Lindsay G Horton,Krista M Delahunty,Harold F Coombs,Leah R Donahue,Ernesto Canalis,Clifford J Rosen,

Genetic analyses with mouse congenic strains for distal Chr1 have identified three closely linked QTLs regulating femoral vBMD, mid-diaphyseal cortical thickness, and trabecular microstructure in a sex-dependent fashion. The homologous relationship between distal mouse Chr 1 and human 1q21-24 offers the possibility of finding common regulatory genes for cortical and trabecular bone. INTRODUCTION: The distal third of mouse chromosome 1 (Chr 1) has been shown to carry a major quantitative trait locus (QTL) for BMD from several inbred mouse strain crosses. Genetic and functional analyses are essential to identify genes and cellular mechanisms for acquisition of peak bone mass. MATERIALS AND METHODS: Nested congenic sublines of mice were developed with a C57BL/6J (B6) background carrying <1- to 9-Mbp-sized segments donated from C3H/HeJ (C3H). Isolated femurs from 16-wk-old female and male mice were measured by pQCT and microCT40 for volumetric (v)BMD, mid-diaphyseal cortical thickness, and distal trabecular phenotypes. Static and dynamic histomorphologic data were obtained on selected females and males at 16 wk. RESULTS AND CONCLUSIONS: We found that the original BMD QTL, Bmd5, mapped to distal Chr 1 consists of three QTLs with different effects on vBMD and trabecular bone in both sexes. Compared with B6 controls, femoral vBMD, BMD, and cortical thickness (p < 0.0001) were significantly increased in congenic subline females, but not in males, carrying C3H alleles at QTL-1. Both females and males carrying C3H alleles at QTL-1 showed marked increases in BV/TV by microCT compared with B6 mice (p < 0.0001). Females increased BV/TV by increasing trabecular thickness, whereas males increased trabecular number. In addition, the microCT40 data showed two unique QTLs for male trabecular bone, QTL-2 and QTL-3, which may interact to regulate trabecular thickness and number. These QTLs are closely linked with and proximal to QTL-1. The histomorphometric data revealed sex-specific differences in cellular and bone formation parameters. Mice and humans share genetic homology between distal mouse Chr 1 and human Chr 1q20-24 that is associated with adult human skeletal regulation. Sex- and compartment-specific regulatory QTLs in the mouse suggest the need to partition human data by sex to improve accuracy of mapping and genetic loci identification.

Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Publishing Authors By Initials

WG Beamer,KL Shultz,CL Ackert-Bicknell,LG Horton,KM Delahunty,HF Coombs,LR Donahue,E Canalis,CJ Rosen,

For similar reproductive and urinary physiology: reproduction: sex characteristics research abstracts see: reproductive and urinary physiology: reproduction: sex characteristics research

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Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of bone and mineral research : the officia

VOLUME: 22

Page Numbers: 1187-96

Journal Abbreviation: J. Bone Miner. Res.

ISSN: 0884-0431

DAY: 3

MONTH: Aug

YEAR: 2007

Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Information

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LANGUAGE: eng

NlmUniqueID: 8610640

Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes. Keywords Mesh Terms:

KEYWORDS: Sex Characteristics

MESH TERMS: genetics

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Grant and Affiliation Information for Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs with sex-dependent regulation of bone phenotypes.

AFFILIATION: The Jackson Laboratory, Bar Harbor, Maine, USA. wesley.beamer@jax.org

Country: United States

AGENCY: United States NEI

GRANT: EY015073

ACRONYM: EY

MEDLINETA: J Bone Miner Res

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