KMT5B is required for early motor development.
KMT5B is required for early motor development.
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DOI：
10.3389/fgene.2022.901228
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发表时间：
2022
影响因子：
3.7
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中科院分区：
文献类型：
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赖氨酸甲基转移酶5 B（KMT 5 B/SUV 4 - 20 H1）中的破坏性变体已被鉴定为在具有神经发育表型包括运动缺陷（即，张力减退和运动延迟）。然而，这种酶在早期运动发育中的作用在很大程度上是未知的。使用Kmt 5 b基因诱捕小鼠模型，我们评估了神经肌肉力量、骨骼肌重量（即，肌肉质量）、神经肌肉接头（NMJ）结构和肌纤维类型、大小和分布。在发育时间（出生后第17天和第44天）进行测试，以代表出生后与成人结构中的慢肌和快肌类型。在青春期开始之前，与野生型男性相比，杂合子男性的慢缩肌重量显著降低，但女性则没有。在年轻的成年阶段，我们确定了减少神经肌肉力量，骨骼肌重量减少（慢肌和快肌），增加NMJ碎片（慢肌），和较小的肌纤维在两种性别。我们得出结论，Kmt 5 b单倍不足导致骨骼肌发育缺陷，导致肌肉质量和体重减少。
Disruptive variants in lysine methyl transferase 5B (KMT5B/SUV4-20H1) have been identified as likely-pathogenic among humans with neurodevelopmental phenotypes including motor deficits (i.e., hypotonia and motor delay). However, the role that this enzyme plays in early motor development is largely unknown. Using a Kmt5b gene trap mouse model, we assessed neuromuscular strength, skeletal muscle weight (i.e., muscle mass), neuromuscular junction (NMJ) structure, and myofiber type, size, and distribution. Tests were performed over developmental time (postnatal days 17 and 44) to represent postnatal versus adult structures in slow- and fast-twitch muscle types. Prior to the onset of puberty, slow-twitch muscle weight was significantly reduced in heterozygous compared to wild-type males but not females. At the young adult stage, we identified decreased neuromuscular strength, decreased skeletal muscle weights (both slow- and fast-twitch), increased NMJ fragmentation (in slow-twitch muscle), and smaller myofibers in both sexes. We conclude that Kmt5b haploinsufficiency results in a skeletal muscle developmental deficit causing reduced muscle mass and body weight.