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Myosin-X knockout is semi-lethal and demonstrates that myosin-X functions in neural tube closure, pigmentation, hyaloid vasculature regression, and filopodia formation.

Ernest G Heimsath | Yang-In Yim | Mirna Mustapha | John A Hammer | Richard E Cheney
Scientific reports | 2017

Myosin-X (Myo10) is an unconventional myosin best known for its striking localization to the tips of filopodia. Despite the broad expression of Myo10 in vertebrate tissues, its functions at the organismal level remain largely unknown. We report here the generation of KO-first (Myo10 tm1a/tm1a ), floxed (Myo10 tm1c/tm1c ), and KO mice (Myo10 tm1d/tm1d ). Complete knockout of Myo10 is semi-lethal, with over half of homozygous KO embryos exhibiting exencephaly, a severe defect in neural tube closure. All Myo10 KO mice that survive birth exhibit a white belly spot, all have persistent fetal vasculature in the eye, and ~50% have webbed digits. Myo10 KO mice that survive birth can breed and produce litters of KO embryos, demonstrating that Myo10 is not absolutely essential for mitosis, meiosis, adult survival, or fertility. KO-first mice and an independent spontaneous deletion (Myo10 m1J/m1J ) exhibit the same core phenotypes. During retinal angiogenesis, KO mice exhibit a ~50% decrease in endothelial filopodia, demonstrating that Myo10 is required to form normal numbers of filopodia in vivo. The Myo10 mice generated here demonstrate that Myo10 has important functions in mammalian development and provide key tools for defining the functions of Myo10 in vivo.

Pubmed ID: 29229982

Associated grants

  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC003299
  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC009590
  • Agency: NCI NIH HHS, United States
    Id: T32 CA009156

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Knockout Mouse Project Repository (tool)

RRID:SCR_007318

Repository of mouse vectors, ES cells, mice, embryos, and sperm generated by NIH KOMP Mutagenesis Project. In addition, KOMP Repository offers services in support of KOMP products, including ES cell microinjection, vector cloning, post-insertional modification of cloned ES cells, cryopreservation, assisted reproduction techniques (IVF, ICSI) and mouse breeding, pathology services, phenotyping services, etc. KOMP Repository is final component of more than $50 million trans-NIH initiative to increase availability of genetically altered mice and related materials. The University of California, Davis (UC Davis) and Children''s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., are collaborating to preserve, protect, and make available about 8,500 types of knockout mice and related products available to research community. Products are generated by two KOMP mutagenesis teams (CSD consortium and Regeneron Inc). All KOMP products generated by CSD consortium and Regeneron are available through KOMP Repository. Notice as of December 19, 2019: Materials from KOMP Repository have been deposited into MMRRC, including all mouse models and mouse embryonic stem cell lines. Eventually www.komp.org will be sunsetting, and IMSR will remove KOMP Repository listings, since they were double listed in MMRRC. MMRRC will contain the most accurate and up to date resource models.

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Molecular Probes (tool)

RRID:SCR_013318

An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.

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International Mouse Phenotyping Consortium (IMPC) (tool)

RRID:SCR_006158

Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6N (tool)

RRID:MGI:2159965

laboratory mouse with name C57BL/6N from MGI.

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B6N.FVB-Tmem163Tg(ACTB-cre)2Mrt/CjDswJ (organism)

RRID:IMSR_JAX:019099

Mus musculus with name B6N.FVB-Tmem163Tg(ACTB-cre)2Mrt/CjDswJ from IMSR.

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B6.Cg-Myo10m1J/GrsrJ (organism)

RRID:IMSR_JAX:024583

Mus musculus with name B6.Cg-Myo10m1J/GrsrJ from IMSR.

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Mutant Mouse Resource and Research Center (biomaterial supply resource)

RRID:SCR_002953

National public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.

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