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I型碘甲状腺原氨酸5'脱碘酶缺乏的近交系小鼠的生理学和遗传学分析。

Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5' deiodinase deficiency.

作者信息

Berry M J, Grieco D, Taylor B A, Maia A L, Kieffer J D, Beamer W, Glover E, Poland A, Larsen P R

机构信息

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

出版信息

J Clin Invest. 1993 Sep;92(3):1517-28. doi: 10.1172/JCI116730.

DOI:10.1172/JCI116730
PMID:8104199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC288298/
Abstract

Inbred mouse strains differ in their capacity to deiodinate iododioxin and iodothyronines, with strains segregating into high or low activity groups. Metabolism of iododioxin occurs via the type I iodothyronine 5'deiodinase (5'DI), one of two enzymes that metabolize thyroxine (T4) to 3,5,3'-triiodothyronine (T3). Recombinant inbred strains derived from crosses between high and low activity strains exhibit segregation characteristic of a single allele difference. Hepatic and renal 5'DI mRNA in a high (C57BL/6J) and low (C3H/HeJ) strain paralleled enzyme activity and concentration, in agreement with a recent report. 5'DI-deficient mice had twofold higher serum free T4 but normal free T3 and thyrotropin. Brown adipose tissue 5'DII was invariant between the two strains. Southern analyses using a 5'DI probe identified a restriction fragment length variant that segregated with 5'DI activity in 33 of 35 recombinant inbred strains derived from four different pairs of high and low activity parental strains. Recombination frequencies using previously mapped loci allowed assignment of the 5'DI gene to mouse chromosome 4 and identified its approximate chromosomal position. We propose the symbol Dio1 to denote the mouse 5'DI gene. Conserved linkage between this segment of mouse chromosome 4 and human HSA1p predicts this location for human Dio1.

摘要

近交系小鼠在脱碘二恶英和碘甲状腺原氨酸的能力上存在差异，这些品系可分为高活性或低活性组。二恶英的代谢是通过I型碘甲状腺原氨酸5'-脱碘酶（5'DI）进行的，该酶是将甲状腺素（T4）代谢为3,5,3'-三碘甲状腺原氨酸（T3）的两种酶之一。由高活性和低活性品系杂交产生的重组近交系表现出单等位基因差异的分离特征。与最近的一份报告一致，高活性品系（C57BL/6J）和低活性品系（C3H/HeJ）的肝脏和肾脏5'DI mRNA与酶活性和浓度平行。5'DI缺陷型小鼠的血清游离T4水平高出两倍，但游离T3和促甲状腺激素水平正常。两种品系之间棕色脂肪组织中的5'DII没有变化。使用5'DI探针进行的Southern分析在来自四对不同的高活性和低活性亲本品系的35个重组近交系中的33个中鉴定出一个与5'DI活性分离的限制性片段长度变体。利用先前定位的基因座的重组频率将5'DI基因定位到小鼠4号染色体上，并确定了其大致的染色体位置。我们建议用符号Dio1来表示小鼠的5'DI基因。小鼠4号染色体的这一片段与人类HSA1p之间的保守连锁预测了人类Dio1的这一位置。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/995f1c24e18a/jcinvest00041-0419-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/f9840e4a86d4/jcinvest00041-0417-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/995f1c24e18a/jcinvest00041-0419-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/f9840e4a86d4/jcinvest00041-0417-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/02310c0d6ffb/jcinvest00041-0417-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/d671dda3e1e9/jcinvest00041-0417-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/dca0ac7985d7/jcinvest00041-0417-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/d2a20ebd3b2f/jcinvest00041-0417-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/288298/995f1c24e18a/jcinvest00041-0419-a.jpg

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