TY - JOUR
T1 - KMT5B is required for early motor development
AU - Hulen, Jason
AU - Kenny, Dorothy
AU - Black, Rebecca
AU - Hallgren, Jodi
AU - Hammond, Kelley G.
AU - Bredahl, Eric C.
AU - Wickramasekara, Rochelle N.
AU - Abel, Peter W.
AU - Stessman, Holly A.F.
N1 - Funding Information:
We thank A. Keefe for helpful discussions related to this work. This research was partially conducted using the Histology Core and Integrated Biomedical Imaging Facility (IBIF) at Creighton University, Omaha, NE. The IBIF facility is supported by the Creighton University School of Medicine and grants GM103427 and GM139762 from NIGMS. The facility was constructed with support from grants from the National Center for Research Resources (RR016469) and the NIGMS (GM103427).
Funding Information:
This work was funded by the LB692 (HS) and LB595 (PWA) Nebraska Tobacco Settlement Biomedical Research Development Program and the Simons Foundation Autism Research Initiative-Bridge to Independence Award (SFARI 381192) to HS. Additional funding was provided by the NIGMS (5P30GM110768-05; PD: Shelley Smith) to HS.
Funding Information:
This work was funded by the LB692 (HS) and LB595 (PWA) Nebraska Tobacco Settlement Biomedical Research Development Program and the Simons Foundation Autism Research Initiative-Bridge to Independence Award (SFARI 381192) to HS. Additional funding was provided by the NIGMS (5P30GM110768-05; PD: Shelley Smith) to HS.
Publisher Copyright:
Copyright © 2022 Hulen, Kenny, Black, Hallgren, Hammond, Bredahl, Wickramasekara, Abel and Stessman.
PY - 2022/8/12
Y1 - 2022/8/12
N2 - 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.
AB - 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.
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U2 - 10.3389/fgene.2022.901228
DO - 10.3389/fgene.2022.901228
M3 - Article
AN - SCOPUS:85136637944
VL - 13
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 901228
ER -