Quantitative Trait Loci Analysis of Tail Tendon Break Time in Mice of C57BL/6J and DBA/2J Lineage

Abstract

Tail tendon break time (TTBT), a measure of collagen cross-linking, shown to increase with age differs significantly among inbred strains of mice, indicating underlying genetic influences. This study was aimed to identify quantitative trait loci (QTLs) associated with tail tendon break time at three ages (200, 500, and 800 days of age) for 23 BxD recombinant inbred strains of mice and B6D2F(2) mice derived from C57BL/6J and DBA/2J strains. Heritability estimates were calculated, and QTL analyses were conducted using interval-mapping methods. Mean tail tendon break time values were higher in males and increased nonlinearly with age. Eight total QTLs were nominated in the B6D2F(2) mice at the three measured ages, with the QTL at 800 days confirmed in the recombinant inbred strains. Allelic effect modeling for the identified QTLs suggests differences in gene action between sexes. Candidate genes in the QTL regions include collagen genes and an advanced glycation end-product receptor. The QTLs identified demonstrate influence at some but not all ages.

Body weight and high‐fat diet are associated with epigenetic aging in female members of the BXD murine family

“…The D2 strain is considered to have a more accelerated aging profile, and has consistently shorter life span than B6 (Yuan, Peters, & Paigen, 2011; Yuan et al, 2009). Other age‐associated parameters include rapid thymic involution (Hsu, Li, Zhang, & Mountz, 2005), quicker replicative senescence of hematopoietic stem cells (De Haan & Van Zant, 1999), and increased tail tendon breakage in D2 compared to B6 (Sloane et al, 2011). Due to random assortment of gene variants, the progeny BXDs have a greater range of variation in life span and aging traits (De Haan & Van Zant, 1999; Roy et al, 2019), and provide a unique resource with which to dissect the interrelations between epigenetic aging and longevity.…”

Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray

“…In the case of B6 and D2, the two strains are highly divergent in a number of complex phenotypes ranging from behavioral and physiological to aging traits. The panel of recombinant inbred progeny derived from B6 and D2 (the BXD panel) has been used extensively in genetic research [ 57 – 61 ]. If there is indeed a distinct profile in DNA methylation between B6 and D2, then it will be of interest to evaluate if it segregates in the BXDs and how the methylome contributes to some of the phenotypic differences.…”

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

“…Tail tendon explant models arguably provide the most reproducible and human-relevant in vitro models of tendon physiology that are available [75][76][77][78][79]. Regarding mechanical properties, rodent fascicles range in elastic modulus from several hundred MPa to over 1 GPa, depending on the anatomical location of tissue harvest, as well as the age, breed, sex, and/or diet of the animal [80][81][82][83][84]. The failure properties of isolated tail tendon fascicles reflect those of whole tendon, with failure stresses on the order of 80 MPa and failure strains of approximately 10% [72].…”