AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice

Guidi, Luiz G.; Holloway, Zoe G.; Arnoult, Christophe; Ray, Pierre F.; Monaco, Anthony P.; Molnár, Zoltán; Velayos‐Baeza, Antonio

doi:10.1038/s41598-018-28666-6

Cited by 17 publications

(12 citation statements)

References 79 publications

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“…Our HTS data ( Table 5 ) were consistent with the modest obesity observed in Igfbp2 KO mice at 8 weeks of age 145 and with IMPC HTS data showing increased body fat in AU040320 KO mice. Male infertility, but no body fat data, was reported in an independent AU040320 KO line, 146 consistent with the male infertility of KO mice studied by both the IMPC and Lexicon. Our HTS data were also consistent with the ability of ADM2 to inhibit HFD-induced obesity when overexpressed by adipose tissue of transgenic mice 147 , 148 and to inhibit food intake when delivered subcutaneously to WT mice, 149 and with the increased BW of Adm2 HET mice.…”

Section: Resultssupporting

confidence: 77%

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Powell¹,

Revelli²,

Doree³

et al. 2021

DMSO

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Purpose Obesity is a major public health problem. Understanding which genes contribute to obesity may better predict individual risk and allow development of new therapies. Because obesity of a mouse gene knockout (KO) line predicts an association of the orthologous human gene with obesity, we reviewed data from the Lexicon Genome5000 TM high throughput phenotypic screen (HTS) of mouse gene KOs to identify KO lines with high body fat. Materials and Methods KO lines were generated using homologous recombination or gene trapping technologies. HTS body composition analyses were performed on adult wild-type and homozygous KO littermate mice from 3758 druggable mouse genes having a human ortholog. Body composition was measured by either DXA or QMR on chow-fed cohorts from all 3758 KO lines and was measured by QMR on independent high fat diet-fed cohorts from 2488 of these KO lines. Where possible, comparisons were made to HTS data from the International Mouse Phenotyping Consortium (IMPC). Results Body fat data are presented for 75 KO lines. Of 46 KO lines where independent external published and/or IMPC KO lines are reported as obese, 43 had increased body fat. For the remaining 29 novel high body fat KO lines, Ksr2 and G2e3 are supported by data from additional independent KO cohorts, 6 ( Asnsd1, Srpk2, Dpp8, Cxxc4, Tenm3 and Kiss1 ) are supported by data from additional internal cohorts, and the remaining 21 including Tle4, Ak5, Ntm, Tusc3, Ankk1, Mfap3l, Prok2 and Prokr2 were studied with HTS cohorts only. Conclusion These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for Ksr2 and G2e3 KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.

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Section: Resultssupporting

confidence: 77%

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Powell¹,

Revelli²,

Doree³

et al. 2021

DMSO

View full text Add to dashboard Cite

show abstract

“…In round spermatids, proacrosomal vesicles accumulate close to the acroplaxome but fail to fuse into a single acrosomal vesicle. These results suggest that AU040320 may be necessary for the normal formation of proacrosomal vesicles or the recruitment of cargo proteins required for downstream events leading to acrosomal fusion [39]. Interestingly, 23 new proteins were identified in the interactome by the software.…”

Section: Golgi Transport Interactomementioning

confidence: 95%

“…Mutant mouse models involving genes encoding these proteins show defects in the acrosome when vesicle formation and trafficking from the trans-Golgi is impaired, as is the case for mutations disrupting Pick1, Gopc, Vps54, Hrb, Sirt1, and other genes. Moreover, the defect can be at the level of fusion of vesicles, as is the case for disruption of Gm130 [38] and AU040320 [39]. There has been a limited number of studies focusing on the interaction and regulation among these proteins.…”

Section: Acrosome Developmentmentioning

confidence: 99%

Sperm Differentiation: The Role of Trafficking of Proteins

Teves

Roldán

Krapf

et al. 2020

IJMS

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Sperm differentiation encompasses a complex sequence of morphological changes that takes place in the seminiferous epithelium. In this process, haploid round spermatids undergo substantial structural and functional alterations, resulting in highly polarized sperm. Hallmark changes during the differentiation process include the formation of new organelles, chromatin condensation and nuclear shaping, elimination of residual cytoplasm, and assembly of the sperm flagella. To achieve these transformations, spermatids have unique mechanisms for protein trafficking that operate in a coordinated fashion. Microtubules and filaments of actin are the main tracks used to facilitate the transport mechanisms, assisted by motor and non-motor proteins, for delivery of vesicular and non-vesicular cargos to specific sites. This review integrates recent findings regarding the role of protein trafficking in sperm differentiation. Although a complete characterization of the interactome of proteins involved in these temporal and spatial processes is not yet known, we propose a model based on the current literature as a framework for future investigations.

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“…Gba2 , Pick1 and Gopc ) ( Xiao et al, 2009 ; Yao et al, 2002 ; Yildiz et al, 2006 ), fusion of the proacrosomal granules to form the acrosome [e.g. Vps54 , Hrb ( Agfg1 ) and AU040320 ] ( Guidi et al, 2018 ; Kang-Decker et al, 2001 ; Paiardi et al, 2011 ) and anchoring the acrosome to the nucleus [e.g. Dpy19l2 , Zpbp1 ( Zpbp ) and Spaca1 ] ( Fujihara et al, 2012 ; Lin et al, 2007 ; Pierre et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

FAM71F1 binds to RAB2A and RAB2B and is essential for acrosome formation and male fertility in mice

et al. 2021

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The acrosome is a cap-shaped, Golgi-derived membranous organelle that is located over the anterior of the sperm nucleus and highly conserved throughout evolution. Although morphological changes during acrosome biogenesis in spermatogenesis have been well described, the molecular mechanism underlying this process is still largely unknown. Family with sequence similarity 71, member F1 and F2 (FAM71F1 and FAM71F2) are testis-enriched proteins that contain a RAB2B-binding domain, a small GTPase involved in vesicle transport and membrane trafficking. Here, by generating mutant mice for each gene, we found that Fam71f1 is essential for male fertility. In Fam71f1-mutant mice, the acrosome was abnormally expanded at the round spermatid stage, likely because of enhanced vesicle trafficking. Mass spectrometry analysis after immunoprecipitation indicated that, in testes, FAM71F1 binds not only RAB2B, but also RAB2A. Further study suggested that FAM71F1 binds to the GTP-bound active form of RAB2A/B, but not the inactive form. These results indicate that a complex of FAM71F1 and active RAB2A/B suppresses excessive vesicle trafficking during acrosome formation.

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AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice

Cited by 17 publications

References 79 publications

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

High-Throughput Screening of Mouse Gene Knockouts Identifies Established and Novel High Body Fat Phenotypes

Sperm Differentiation: The Role of Trafficking of Proteins

FAM71F1 binds to RAB2A and RAB2B and is essential for acrosome formation and male fertility in mice

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