RGD Reference Report - Biallelic mutations in MOS cause female infertility characterized by human early embryonic arrest and fragmentation. - Rat Genome Database

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Biallelic mutations in MOS cause female infertility characterized by human early embryonic arrest and fragmentation.

Authors: Zhang, Yin-Li  Zheng, Wei  Ren, Peipei  Hu, Huiling  Tong, Xiaomei  Zhang, Shuo-Ping  Li, Xiang  Wang, Haichao  Jiang, Jun-Chao  Jin, Jiamin  Yang, Weijie  Cao, Lanrui  He, Yuanlin  Ma, Yerong  Zhang, Yingyi  Gu, Yifan  Hu, Liang  Luo, Keli  Gong, Fei  Lu, Guang-Xiu  Lin, Ge  Fan, Heng-Yu  Zhang, Songying 
Citation: Zhang YL, etal., EMBO Mol Med. 2021 Dec 7;13(12):e14887. doi: 10.15252/emmm.202114887. Epub 2021 Nov 15.
RGD ID: 596933304
Pubmed: PMID:34779126   (View Abstract at PubMed)
PMCID: PMC8649871   (View Article at PubMed Central)
DOI: DOI:10.15252/emmm.202114887   (Journal Full-text)

Early embryonic arrest and fragmentation (EEAF) is a common phenomenon leading to female infertility, but the genetic determinants remain largely unknown. The Moloney sarcoma oncogene (MOS) encodes a serine/threonine kinase that activates the ERK signaling cascade during oocyte maturation in vertebrates. Here, we identified four rare variants of MOS in three infertile female individuals with EEAF that followed a recessive inheritance pattern. These MOS variants encoded proteins that resulted in decreased phosphorylated ERK1/2 level in cells and oocytes, and displayed attenuated rescuing effects on cortical F-actin assembly. Using oocyte-specific Erk1/2 knockout mice, we verified that MOS-ERK signal pathway inactivation in oocytes caused EEAF as human. The RNA sequencing data revealed that maternal mRNA clearance was disrupted in human mature oocytes either with MOS homozygous variant or with U0126 treatment, especially genes relative to mitochondrial function. Mitochondrial dysfunction was observed in oocytes with ERK1/2 deficiency or inactivation. In conclusion, this study not only uncovers biallelic MOS variants causes EEAF but also demonstrates that MOS-ERK signaling pathway drives human oocyte cytoplasmic maturation to prevent EEAF.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MOSHumanFemale Infertility  IAGP DNA:mutations: :RGD 
MosRatFemale Infertility  ISOMOS (Homo sapiens)DNA:mutations: :RGD 
MosMouseFemale Infertility  ISOMOS (Homo sapiens)DNA:mutations: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mos  (MOS proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Mos  (Moloney sarcoma oncogene)

Genes (Homo sapiens)
MOS  (MOS proto-oncogene, serine/threonine kinase)


Additional Information