Mice deficient in APOBEC2 and APOBEC3
Mice deficient in APOBEC2 and APOBEC3
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DOI：
10.1128/mcb.25.16.7270-7277.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Rada, C
中科院分区：
文献类型：
--
作者：
Mikl, MC;Watt, IN;Rada, C
活化诱导的脱氨酶/载脂蛋白B编辑催化亚基1（AID/APOBEC）家族包括四组蛋白质。AID是一种淋巴特异性DNA脱氨酶，可触发抗体多样化，APOBEC 2（功能未知）在所有检查的脊椎动物中均有发现。相比之下，APOBEC 1（胃肠道细胞中的RNA编辑酶）和APOBEC 3仅限于哺乳动物。大多数APOBEC 3的功能，其中有七个在人类中，但在小鼠中的一个，是未知的，虽然几个人APOBEC 3作为宿主限制因子，脱氨人类免疫缺陷病毒I型复制中间体。然而，已经提出了APOBEC 3在保护免受内源性逆转录因子转座中的更原始的功能。在这里，我们专注于小鼠APOBEC 2（一种肌肉特异性蛋白质，我们没有发现对胞苷脱氨活性的证据，无论是作为游离核苷酸还是在DNA中）和小鼠APOBEC 3（一种DNA脱氨酶，我们发现它广泛表达，但在淋巴组织中最丰富）。基因靶向实验表明，APOBEC 2（尽管是该家族的祖先成员，在肌肉中没有明显的冗余）和APOBEC 3（尽管其在限制内源性逆转录转座中的作用）对小鼠发育，存活或生育力都是不必要的。
The activation-induced deaminase/apolipoprotein B-editing catalytic subunit 1 (AID/APOBEC) family comprises four groups of proteins. Both AID, a lymphoid-specific DNA deaminase that triggers antibody diversification, and APOBEC2 (function unknown) are found in all vertebrates examined. In contrast, APOBEC1, an RNA-editing enzyme in gastrointestinal cells, and APOBEC3 are restricted to mammals. The function of most APOBEC3s, of which there are seven in human but one in mouse, is unknown, although several human APOBEC3s act as host restriction factors that deaminate human immunodeficiency virus type I replication intermediates. A more primitive function of APOBEC3s in protecting against the transposition of endogenous retroelements has, however, been proposed. Here, we focus on mouse APOBEC2 (a muscle-specific protein for which we find no evidence of a deaminating activity on cytidine whether as a free nucleotide or in DNA) and mouse APOBEC3 (a DNA deaminase which we find widely expressed but most abundant in lymphoid tissue). Gene-targeting experiments reveal that both APOBEC2 (despite being an ancestral member of the family with no obvious redundancy in muscle) and APOBEC3 (despite its proposed role in restricting endogenous retrotransposition) are inessential for mouse development, survival, or fertility.