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INRA
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Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

C-Nap1, from the cow to the mouse, a centriolar protein gradually reveals its secrets

@INRAE - Sandrine Floriot (Impact de la troncation de la protéine C-Nap1 Bovin vs Murin)
A study of the Caprine-like Generalized Hypoplasia Syndrome (SHGC) in the Montbeliard breed identified a mutation leading to the truncation of the C-Nap1 protein. In order to gain knowledge on the role of this protein, we created a murine model containing a similar mutation. The analysis of these mice did not confirm the role of this protein in the appearance of the SHGC syndrome but revealed its role in male fertility.

In the Montbeliard breed, animals with Caprine-like Generalized Hypoplasia Syndrome have a long and thin head, pronounced muscular insufficiency and partial coat depigmentation of the red zones. A mapping study followed by genome sequencing provided evidence of a mutation responsible for a premature stop codon in the the C-Nap1 protein.  This protein plays a role in centrosome cohesion during cell division.

The phenotypes, observed in cattle, are similar to those found in men with Seckel syndrome in which several mutations on genes coding for centrosomal proteins have been found. Due to similarities between SHGC and different syndromes present in man, C-Nap1 protein mutations could be responsable for primary microcephalies or Seckel syndrome.

In order to gain knowledge on the role of this protein, a mouse strain with a similar mutation as that described in cattle, was created using genome editing tools.

Surprisingly, the mice obtained presented none of the phenotypes described previously in cattle but sterility in males, a non-characterized but suspected phenotype in cattle. This infertility was associated with a reduced number of spermatogonia and a blockage of the remaining cells during the first phase of meiosis. An absence of centrosome cohesion was also observed in these progeny cells but do not seem to have an impact on female pathways indicating a normal reproduction in the latter. Other centrosomal proteins also impact male fertility in mice. Our study supports the role of centrosomal proteins in fertility and will lead to new enquiries on their role in morphogenesis in different species.

Scientific contact:

Partners

  • INRAE, AgroParisTech, Université Paris-Saclay, GABI, BREED, Jouy-en-Josas, France
  • Laboratory of Development of the Gonads, UMRE008 Genetic Stability Stem Cells and Radiations, IRCM/IBFJ CEA, Université de Paris, Université Paris-Saclay, Paris, France

See also

References:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423223/ 
Floriot S, Vesque C, Rodriguez S, Bourgain-Guglielmetti F, Karaiskou A, Gautier M, Duchesne A, Barbey S, Fritz S, Vasilescu A, Bertaud M, Moudjou M, Halliez S, Cormier-Daire V, Hokayem JE, Nigg EA, Manciaux L, Guatteo R, Cesbron N, Toutirais G, Eggen A, Schneider-Maunoury S, Boichard D, Sobczak-Thépot J, Schibler L. C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle. Nat Commun. 2015 Apr 23;6:6894. doi: 10.1038/ncomms7894. PMID: 25902731; PMCID: PMC4423223.

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809461/ 
Floriot S, Bellutti L, Castille J, Moison P, Messiaen S, Passet B, Boulanger L, Boukadiri A, Tourpin S, Beauvallet C, Vilotte M, Riviere J, Péchoux C, Bertaud M, Vilotte JL, Livera G. CEP250 is Required for Maintaining Centrosome Cohesion in the Germline and Fertility in Male Mice. Front Cell Dev Biol. 2022 Jan 19;9:754054. doi: 10.3389/fcell.2021.754054. PMID: 35127699; PMCID: PMC8809461.

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