Thyroid Autoimmune Disease Unit, Cedars-Sinai Research Institute and University of California, Los Angeles School of Medicine, Los Angeles, California 90048, USA.
Endocrinology. 2011 Mar;152(3):1172-9. doi: 10.1210/en.2010-1138. Epub 2011 Jan 5.
C3H/He and BALB/c mice have elevated serum thyroxine levels associated with low deiodinase type-1 activity whereas C57BL/6 (B6) mice have low thyroxine levels and elevated deiodinase type-1 activity. High-resolution genetic maps are available for four sets of recombinant inbred (RI) mice derived from B6 parents bred to C3H/He, BALB/c, DBA/2, or A strains. Total and free T4 (T-T4 and F-T4) levels in females from these RI sets (BXH, CXB, BXD, and AXBXA) were analyzed to test two hypotheses: first, serum T4 variability is linked to the deiodinase type-1 gene; second, because of their shared B6 parent, the RI sets will share linkages responsible for T-T4 or F-T4 variability. A number of chromosomes (Chr) and loci were linked to T-T4 (Chr 1, 4, 13, 11) or F-T4 (Chr 1, 6, 13, 18, 19). Linkage between T-T4 and Chr 4 was limited to CXB and BXH strains, but the locus was distinct from the deiodinase type-1 gene. Surprisingly, many linkages were unique providing "genetic signatures" for T-T4 or F-T4 in each set of RI mice. Indeed, the strongest linkage between T-T4 (or F-T4) and a Chr 2 locus (logarithm of the odds scores >4.4) was only observed in AXBXA strains. Some loci corresponded to genes/Chr associated in humans with variable TSH or T-T4 levels. Unlike inbred mice, human populations are extremely diverse. Consequently, our data suggest that the contributions of unique chromosomes/loci controlling T-T4 and F-T4 in distinct human subgroups are likely to be "buried" in genetic analyses of heterogeneous human populations.
C3H/He 和 BALB/c 小鼠的血清甲状腺素水平升高，伴有脱碘酶 1 活性降低，而 C57BL/6（B6）小鼠的甲状腺素水平较低，脱碘酶 1 活性升高。B6 父母与 C3H/He、BALB/c、DBA/2 或 A 品系杂交产生的四组重组近交系（RI）小鼠具有高分辨率的遗传图谱。这些 RI 系（BXH、CXB、BXD 和 AXBXA）雌性的总甲状腺素（T-T4）和游离甲状腺素（F-T4）水平进行了分析，以验证两个假设：第一，血清 T4 变异性与脱碘酶 1 基因有关；第二，由于它们具有共同的 B6 亲本，这些 RI 系将共享导致 T-T4 或 F-T4 变异性的连锁关系。许多染色体（Chr）和基因座与 T-T4（Chr 1、4、13、11）或 F-T4（Chr 1、6、13、18、19）相关联。T-T4 与 Chr 4 之间的连锁仅限于 CXB 和 BXH 品系，但该基因座与脱碘酶 1 基因不同。令人惊讶的是，许多连锁关系是独特的，为每个 RI 系的 T-T4 或 F-T4 提供了“遗传特征”。事实上，在 AXBXA 品系中观察到 T-T4（或 F-T4）与 Chr 2 基因座之间最强的连锁关系（对数优势评分>4.4）。一些基因座与人类中与 TSH 或 T-T4 水平变化相关的基因/Chr 相对应。与近交系小鼠不同，人类群体极其多样化。因此，我们的数据表明，控制不同人类亚群 T-T4 和 F-T4 的独特染色体/基因座的贡献很可能在对异质人类群体的遗传分析中“被掩盖”。
