Developmental dosing with a MEK inhibitor (PD0325901) rescues myopathic features of the muscle-specific but not limb-specific Nf1 knockout mouse.

Molecular Genetics and Metabolism
Matthew A SummersA Schindeler

Abstract

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder While NF1 is primarily associated with predisposition for tumor formation, muscle weakness has emerged as having a significant impact on quality of life. NF1 inactivation is linked with a canonical upregulation Ras-MEK-ERK signaling. This in this study we tested the capacity of the small molecule MEK inhibitor PD0325901 to influence the intramyocellular lipid accumulation associated with NF1 deficiency. Established murine models of tissue specific Nf1 deletion in skeletal muscle (Nf1MyoD-/-) and limb mesenchyme (Nf1Prx1-/-) were tested. Developmental PD0325901 dosing of dams pregnant with Nf1MyoD-/- progeny rescued the phenotype of day 3 pups including body weight and lipid accumulation by Oil Red O staining. In contrast, PD0325901 treatment of 4 week old Nf1Prx1-/- mice for 8 weeks had no impact on body weight, muscle wet weight, activity, or intramyocellular lipid. Examination of day 3 Nf1Prx1-/- pups showed differences between the two tissue-specific knockout strains, with lipid staining greatest in Nf1MyoD-/- mice, and fibrosis higher in Nf1Prx1-/- mice. These data show that a MEK/ERK dependent mechanism underlies NF1 muscle metabolism during dev...Continue Reading

References

Nov 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J E DeClueD R Lowy
Mar 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·D H GutmannD E Wright
Feb 15, 1994·Journal of Neuroscience Research·D H GutmannF S Collins
Jul 21, 1998·Human Molecular Genetics·A KloseP Nürnberg
Jun 21, 2005·Genes & Development·Lina Kassar-DuchossoyShahragim Tajbakhsh
Jul 5, 2006·Seminars in Pediatric Neurology·Terry M LevineLaurie E Cutting
Aug 12, 2008·Seminars in Cell & Developmental Biology·Aaron SchindelerDavid G Little
Nov 4, 2010·Current Neurology and Neuroscience Reports·Wen-Chen Liang, Ichizo Nishino
Apr 12, 2011·Human Molecular Genetics·Nadine KosslerMateusz Kolanczyk
Oct 1, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jad El-HossDavid G Little
Jun 27, 2012·AJR. American Journal of Roentgenology·Neel B Patel, Gregory Scott Stacy
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Aug 22, 2012·Muscle & Nerve·David A StevensonKatherine A Rauen
Sep 1, 2012·Developmental Medicine and Child Neurology·Annukka LehtonenSusan M Huson
Dec 12, 2012·The Journal of Clinical Investigation·Walter J JessenNancy Ratner
Jan 12, 2013·American Journal of Medical Genetics. Part a·Juliana Ferreira de SouzaLuiz Oswaldo Carneiro Rodrigues
Aug 13, 2013·Handbook of Clinical Neurology·Rosalie E Ferner, David H Gutmann
Sep 26, 2013·Proceedings of the National Academy of Sciences of the United States of America·Julia von MaltzahnMichael A Rudnicki
Oct 29, 2013·Human Molecular Genetics·Kate SullivanAaron Schindeler
Apr 17, 2015·Nature Reviews. Cancer·Nancy Ratner, Shyra J Miller
Apr 29, 2015·Developmental Medicine and Child Neurology·Kayla M D CornettJoshua Burns
Dec 12, 2017·Human Molecular Genetics·Matthew A SummersAaron Schindeler

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Citations

Oct 21, 2020·Journal of Cachexia, Sarcopenia and Muscle·Xiaoyan WeiSigmar Stricker
Feb 2, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yoshiko MaedaKatherine A Rauen
Dec 11, 2020·Science Translational Medicine·Behnam RabieeAli R Djalilian

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