We identified quantitative trait loci (QTL) that determined the genetic variance in serum IGF-I through genome-wide scanning of mice derived from C57BL\/6J(B6) x C3H\/HeJ(C3H) intercrosses. One QTL (Igf1s2), on mouse chromosome 10 (Chr10), produces a 15% increase in serum IGF-I in B6C3 F2 mice carrying c3 alleles at that position. We constructed a congenic mouse, B6.C3H-10 (10T), by backcrossing c3 alleles from this 57-Mb region into B6 for 10 generations. 10T mice have higher serum and skeletal IGF-I, greater trabecular bone volume fraction, more trabeculae, and a higher number of osteoclasts at 16 wk, compared with B6 (P < 0.05). Nested congenic sublines generated from further backcrossing of 10T allowed for recombination and produced four smaller sublines with significantly increased serum IGF-I at 16 wk (i.e. 10-4, 10-7, 10-10, and 10-13), compared with B6 (P < 0.0003), and three smaller sublines that showed no differences in IGF-I vs. age- and gender-matched B6 mice. Like 10T, the 10-4 nested sublines at 16 wk had higher femoral mineral (P < 0.0001) and greater trabecular connectivity density with significantly more trabeculae than B6 (P < 0.01). Thus, by comprehensive phenotyping, we were able to narrow the QTL to an 18.3-Mb region containing approximately 148 genes, including Igf1 and Elk-3(ETS domain protein). Allelic differences in the Igf1s2 QTL produce a phenotype characterized by increased serum IGF-I and greater peak bone density. Congenic mice establish proof of concept of shared genetic determinants for both circulating IGF-I and bone acquisition.\n<\/p>\n","protected":false},"excerpt":{"rendered":"
We identified quantitative trait loci (QTL) that determined the genetic variance in serum IGF-I through genome-wide scanning of mice derived<\/p>\n","protected":false},"author":22,"parent":0,"menu_order":0,"template":"","format":"standard","meta":{"_acf_changed":false},"tags":[],"thema":[5866,5920],"produktgruppe":[5825],"literatur_kategorie":[7223],"class_list":["post-163192","literatur","type-literatur","status-publish","format-standard","hentry","thema-diagnostics-using-leonardo-pqct","thema-pre-clinical-research","produktgruppe-pqct-en","literatur_kategorie-pre-clinical-studies"],"acf":[],"_links":{"self":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur\/163192","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur"}],"about":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/types\/literatur"}],"author":[{"embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/users\/22"}],"version-history":[{"count":0,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur\/163192\/revisions"}],"wp:attachment":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/media?parent=163192"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/tags?post=163192"},{"taxonomy":"thema","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/thema?post=163192"},{"taxonomy":"produktgruppe","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/produktgruppe?post=163192"},{"taxonomy":"literatur_kategorie","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur_kategorie?post=163192"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}