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Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model
Published on: September 8, 2023
A novel locus on the X chromosome regulates post-maturity bone density changes in mice
Dorota Szumska1, Helen Benes, Ping Kang
1Department of Geriatrics, University of Arkansas for Medical Sciences, and Central Arkansas Veterans Healthcare Service, Little Rock, AR 72205, USA.
Bone
|December 23, 2006
Summary
Genetic mapping reveals distinct genes controlling bone growth versus remodeling. A novel X-chromosome locus influences age-dependent bone mineral density changes in mice, potentially impacting human skeletal health.
Area of Science:
- Genetics
- Osteology
- Mammalian Biology
Background:
- Bone mineral density (BMD) accrual varies significantly between mouse strains.
- Understanding the genetic basis of bone development and age-related changes is crucial for skeletal health research.
Purpose of the Study:
- To investigate the genetic factors influencing longitudinal bone mineral density (BMD) changes in mice.
- To identify genetic loci associated with skeletal growth and age-dependent BMD variation.
Main Methods:
- Longitudinal assessment of spine BMD in AKR/J and SAMP6 mouse strains and their F(2) progeny.
- Calculation of heritability for the DeltasBMD trait (ratio of 6-month/4-month spine BMDs).
- Genetic mapping to identify loci associated with BMD and DeltasBMD, including analysis of single-nucleotide polymorphisms (SNPs).
Main Results:
- Significant differences in bone accrual patterns were observed between AKR/J and SAMP6 strains.
- Heritability of DeltasBMD was calculated at 0.59, indicating a strong genetic influence.
- Two significant genetic loci were identified: one on the X chromosome influencing age-dependent BMD changes and another on chromosome 7.
Conclusions:
- Different genes regulate skeletal growth versus remodeling.
- An X-chromosome locus identified in mice shows potential synteny with a region linked to lumbar bone density in postmenopausal women.
- Further research into these loci may provide insights into human skeletal disorders.
Related Concept Videos
Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
The Y Chromosome Determines Maleness
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...
Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
X-Inactivation
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.

