{"title":"The complete mitochondrial genome assembly of Bali cattle (Bos javanicus) using Oxford nanopore long-read sequencing technology","authors":"Saiful Anwar , Fajrin Shidiq , Ronny Rachman Noor , Gono Semiadi , Anik Budhi Dharmayanthi , Ahmad Furqon , Isyana Khaerunnisa , Sutikno Sutikno , Endang Tri Margawati , Jakaria Jakaria","doi":"10.1016/j.gene.2025.149706","DOIUrl":"10.1016/j.gene.2025.149706","url":null,"abstract":"<div><div>Bali cattle, domesticated from wild banteng (<em>Bos javanicus</em>), serve as an important indigenous genetic resource in Indonesia. Creating a detailed mitochondrial genome (mitogenome) sequence of Bali cattle is essential for population genetic research and promoting sustainable breeding. This study aimed to assemble the complete mitogenome sequence of Bali cattle, analyze its genetic features, and explore its phylogenetic position within the <em>Bos</em> genus. High-molecular-weight genomic DNA was extracted from the blood of a male Bali cattle, and mitogenome sequencing was performed using Oxford Nanopore long-read sequencing, combining nanopore adaptive sampling (NAS) and amplicon-based sequencing approaches. Both NAS and amplicon-based methods can assemble a complete mitogenome of Bali cattle. However, validating NAS assemblies through amplicon-based sequencing improves accuracy and completeness. The complete mitogenome of Bali cattle spans 16,387 bp, comprising 13 protein-coding genes (PCGs), 22 transfer RNA (<em>tRNA</em>) genes, two ribosomal RNA (<em>rRNA</em>) genes, and a non-coding control region (CR), which showed a structure similar to that observed in other <em>Bos</em> species. Phylogenetic analysis showed that Bali cattle group with <em>B. javanicus</em>, closely related to Javan banteng (<em>B. j. javanicus</em>). Interestingly, a unique tandem repeat sequence was found only in the CR of <em>B. j. javanicus</em>, including Bali cattle. Notably, the current NCBI reference mitogenome for <em>B. javanicus</em> (NC_012706.1) is more closely related to <em>B. taurus</em> than to verified <em>B. javanicus</em> sequences, underscoring the need for a reliable <em>B. javanicus</em>-specific reference mitogenome. This study offers novel insights into the comprehensive mitogenomic architecture of Bali cattle. Furthermore, the discovery of a unique tandem repeat motif offers potential as a marker for Bali cattle identification and its applications in forensic and product authentication.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149706"},"PeriodicalIF":2.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-31DOI: 10.1016/j.gene.2025.149709
Jéssica Andrade Paes , Henrique Bunselmeyer Ferreira
{"title":"Molecular mechanisms of gene expression regulation in Mycoplasma spp.: insights into virulence-related genes","authors":"Jéssica Andrade Paes , Henrique Bunselmeyer Ferreira","doi":"10.1016/j.gene.2025.149709","DOIUrl":"10.1016/j.gene.2025.149709","url":null,"abstract":"<div><div><em>Mycoplasma</em> spp<em>.</em> are genome-reduced bacteria, many of which are pathogenic for humans and livestock. The mechanisms driving host colonization and pathogenicity for mycoplasmas remain only partially understood. These processes are influenced by both genomic factors, such as variations in gene content and organization, and regulatory mechanisms that control the expression of virulence-related genes. This review provides a comprehensive survey of the molecular mechanisms governing gene expression regulation in mycoplasmas, with particular interest on virulence-related genes. Mycoplasmas have undergone reductive and convergent evolutionary processes, which have shaped the distribution of virulence-related genes and the variability in their regulatory sequences, leading to species-specific pathogenic strategies. At the transcriptional level, only a small fraction of genes is regulated by transcription factor binding, suggesting that mycoplasmas rely on alternative regulatory mechanisms, such as supercoiling and chromosome topology. Additionally, gene expression in mycoplasma is regulated at the post-transcriptional level, as evidenced by comparative transcriptomics and proteomics studies. Despite recent advances, significant gaps remain in understanding the specific mechanisms of virulence gene regulation, particularly at the post-transcriptional level. This review highlights the need for further research into the complex interplay between genomic organization and regulatory mechanisms underlying mycoplasma pathogenicity, providing a foundation for future studies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149709"},"PeriodicalIF":2.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-30DOI: 10.1016/j.gene.2025.149708
Rasmita Khatonier , Abdul Mabood Khan
{"title":"Genetic variations in interleukin-17 gene: a review on SNP rs2275913 and its clinical implications","authors":"Rasmita Khatonier , Abdul Mabood Khan","doi":"10.1016/j.gene.2025.149708","DOIUrl":"10.1016/j.gene.2025.149708","url":null,"abstract":"<div><div>Genetic polymorphisms contribute significantly to the wide range of phenotypic diversity and varying disease susceptibility across the human population. Identifying genetic predispositions to diseases can aid in early prevention and treatment strategies. The pro-inflammatory cytokine IL-17 plays a crucial role in several clinical conditions, underscoring the importance of exploring its genetic structure. Cytokines, which regulate the immune system in various ways, are implicated in the pathophysiology of both communicable and non-communicable diseases. This review examines the impact of the SNP rs2275913 in the IL-17 gene on different diseases across diverse global populations. A comprehensive search of electronic databases, including PubMed, Google Scholar, and SNPedia, was conducted to explore studies on polymorphisms. Notably, genetic polymorphisms that affect one population may not be associated with others, and an SNP allele linked to disease progression in one group might act as a protective factor in another. Since most SNPs are known to influence gene expression, protein stability, localization, and function, their influence on cytokine protein levels may regulate the likelihood of disease development. Gene expression is regulated by a complex network of transcriptional activators and repressors, and SNPs can alter this regulation, leading to individual variations. Variations in cytokine genes, such as IL-17, can affect immune response pathways, thereby influencing both disease susceptibility and resistance.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"967 ","pages":"Article 149708"},"PeriodicalIF":2.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-29DOI: 10.1016/j.gene.2025.149702
Yufu Liu , Jiayi Liu , Ruixin Liao , Jianyi Wen , Ying Lei , Wenjing Zhong , Junhui Huo , Zhengliang Ouyang , Wenhua Liu , Ruiai Chen
{"title":"RNA-seq reveals the critical role of the Glaesserella parasuis hfq gene in stress response and virulence","authors":"Yufu Liu , Jiayi Liu , Ruixin Liao , Jianyi Wen , Ying Lei , Wenjing Zhong , Junhui Huo , Zhengliang Ouyang , Wenhua Liu , Ruiai Chen","doi":"10.1016/j.gene.2025.149702","DOIUrl":"10.1016/j.gene.2025.149702","url":null,"abstract":"<div><div>Hfq protein is widely present in most bacteria and participates in regulating the expression of bacterial virulence factors in various gram-negative bacteria. Mutations in the <em>hfq</em> gene lead to decreased bacterial virulence in <em>Glaesserella parasuis</em>. However, the molecular mechanism between Hfq protein and bacterial virulence remains unknown. In this study, an <em>hfq</em> gene in-frame deletion mutant strain was constructed through the natural transformation method, the differences in bacterial biological characteristics between mutant and parent strains were compared, and the changes in bacterial transcriptome caused by <em>hfq</em> gene mutations were determined through RNA-seq. The results revealed that the <em>hfq</em> gene mutation did not alter the bacterial growth rate or morphology. However, the Δ<em>hfq</em> mutant exhibited significantly reduced survival under stress conditions, including 42 °C heat shock, 100 mM H<sub>2</sub>O<sub>2</sub>, 8 mM HCl, and iron-deficient environments, compared with the parent strain. Moreover, the mutation led to attenuated bacterial virulence in the mouse infection model. RNA-seq results revealed that the different expressed genes are involved in the stress response, iron ion metabolism, and transcriptional regulation, and some potential virulence factors, such as <em>sodA</em> and <em>rpoC</em> in <em>Glaesserella parasuis</em> were downregulated. Overall, these findings provide preliminary insights into the molecular mechanism between Hfq protein, stress response, and bacterial virulence.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149702"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the role of a novel hemizygous FAAH2 variant in neurological and metabolic disorders","authors":"Mirella Vinci , Donatella Greco , Simone Treccarichi , Antonino Musumeci , Angelo Gloria , Concetta Federico , Salvatore Saccone , Francesco Calì , Sandra Sirrs","doi":"10.1016/j.gene.2025.149703","DOIUrl":"10.1016/j.gene.2025.149703","url":null,"abstract":"<div><div>Fatty acid amide hydrolase 2 (FAAH2) is an enzyme involved in the degradation of endocannabinoids in humans. Altered FAAH2 activity has been implicated in various neurological and psychiatric conditions. We describe a male patient presenting with anxiety disorder, autistic-like traits, and borderline intellectual functioning (BIF), as well as metabolic disturbances including obesity and hepatic steatosis. Trio-based whole-exome sequencing (WES) identified the novel hemizygous c.988C > A (p.Gln330Lys) variant in the X-linked <em>FAAH2</em> gene, which currently lacks an associated MIM phenotype. Structural modelling suggested that the variant induces multiple alterations in the amidase signature (AS), a key functional domain of the enzyme. These findings contribute to the emerging evidence supporting <em>FAAH2</em> as a candidate gene for a neurodevelopmental phenotype with metabolic involvement, consistent with an X-linked inheritance pattern.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149703"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-29DOI: 10.1016/j.gene.2025.149704
Yujun Sun , Yali Fan , Yuxiao Li , Zhi Zheng , Lin He , Mingwei Xin , Lin Li
{"title":"Sequence variant of POU5F1 as risk factor for premature ovarian insufficiency by mis-regulating transcription","authors":"Yujun Sun , Yali Fan , Yuxiao Li , Zhi Zheng , Lin He , Mingwei Xin , Lin Li","doi":"10.1016/j.gene.2025.149704","DOIUrl":"10.1016/j.gene.2025.149704","url":null,"abstract":"<div><div>Premature ovarian insufficiency (POI) is a severe disease that leads to female infertility. Previous studies have suggested that genetic mutations are one of the causes of POI. In order to explore novel pathogenic genes associated with POI, we performed whole-exome sequencing on 111 patients with POI. A rare stop codon variant (NM_002701: c.876 T > G: p.Y292*) of the <em>POU5F1</em> gene was identified in one patient. The <em>POU5F1</em> gene encodes the OCT4 protein, which has been reported to play an essential role in the specification and proliferation of primordial germ cells. In this study, we constructed wild-type (WT) and truncated mutant plasmids of the <em>POU5F1</em> gene, transfected cells with them respectively, and carried out RNA sequencing analysis. We found that 681 genes were differentially expressed between the groups expressing the <em>POU5F1</em>-WT and truncated mutant plasmids. Gene ontology analysis revealed that these genes were enriched in biological processes such as germ cell development, gonadal development, follicle-regulated growth to maturity, ovulation from ovarian follicle, and negative regulation of the BMP signaling pathway. Quantitative real-time PCR confirmed that the genes <em>LIN28A, NANOG, TRIM49D1, FRG2C, KLHL10</em>, and <em>HOXB4</em> were significantly differentially expressed between the groups expressing the <em>POU5F1</em>-WT and truncated mutant plasmids. This study is the first to discover that the <em>POU5F1</em> gene may be associated with POI, and suggests that the rare truncated mutation of the <em>POU5F1</em> gene may be one of the genetic pathogenic factors of POI.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149704"},"PeriodicalIF":2.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of the Rs2070075 GALT gene variant with Iranian primary ovarian insufficiency patients","authors":"Farzaneh Adibi , Parnaz Borjian Boroujeni , Azadeh Ghaheri , Mehri Mashayekhi , Navid Almadani , Masood Bazrgar","doi":"10.1016/j.gene.2025.149683","DOIUrl":"10.1016/j.gene.2025.149683","url":null,"abstract":"<div><h3>Purpose</h3><div>Primary ovarian insufficiency (POI) is ovarian follicle deficiency causing menstruation interruption before 40. <em>GALT</em> gene’s defect can lead to POI besides galactosemia. Due to the association of <em>GALT</em>’s rs75391579 variant with POI in galactosemia and its presence in the Iranian general population, we aimed to determine its association with POI in Iranian patients.</div></div><div><h3>Materials and methods</h3><div>The blood DNA of 100 idiopathic POI patients underwent Polymerase Chain Reaction (PCR) and Sanger sequencing. Chi-square test was used as statistical analysis (p-value < 0.05). Frequencies were compared to Iranome database as the Iranian general population, and with Minor Allele Frequency (MAF) and the Highest MAF.</div></div><div><h3>Results</h3><div>The exonic rs2070075 C > T, and the intronic rs2277202 and rs41274867 G > A variants were detected. The genotype and allele frequencies of the rs2070075 were significantly different from the Highest MAF (p = 0.037, p = 0.011). The variants rs2277202 and rs41274867 showed significant differences compared to MAF (p-value < 0.001), but not when compared to Iranome and the highest MAF. The rs75391579 was not found in the studied patients.</div></div><div><h3>Conclusion</h3><div>The homozygous TT genotype of rs2070075 in one patient, whose mother with the same genotype experienced early menopause at 39, seems correlated with Iranian POI patients. As the rs2070075 has not been reported in POI so far, further investigation is recommended.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149683"},"PeriodicalIF":2.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-26DOI: 10.1016/j.gene.2025.149686
Jiaqiong Lin , Yan Lin , Xueyi Jian , Xiaoyong Li
{"title":"Multi-gene anoikis signature combined with tumor microenvironment stratifies prognosis in cutaneous melanoma with experimental validation of PTK6","authors":"Jiaqiong Lin , Yan Lin , Xueyi Jian , Xiaoyong Li","doi":"10.1016/j.gene.2025.149686","DOIUrl":"10.1016/j.gene.2025.149686","url":null,"abstract":"<div><h3>Background</h3><div>Cutaneous melanoma (CM) exhibits aggressive behavior driven by anoikis resistance and dysregulated tumor microenvironment (TME). The combined prognostic value of anoikis susceptibility and immune landscape remains uncharacterized.</div></div><div><h3>Methods</h3><div>Using transcriptomic data from 471 TCGA-CM patients, we developed an 11-gene anoikis risk score (RS) through LASSO-Cox regression, with external validation in the GSE65904 cohort (n = 214). This risk score was integrated with ESTIMATE-quantified immune/stromal features to construct the RS-TME classifier. Functional validation focused on Protein Tyrosine Kinase 6 (PTK6), a key prognostic driver, employing in vitro and in vivo models.</div></div><div><h3>Results</h3><div>We established an 11-gene RS with superior predictive capacity compared to conventional clinical indicators. Consensus clustering identified two molecular subtypes where Cluster B showed significantly improved survival compared to Cluster A (p < 0.001). Single-cell RNA sequencing confirmed immune cells, particularly macrophages, possessed substantially higher anoikis scores than malignant cells. This microenvironment foundation guided development of the RS-TME classifier, which stratified patients into three prognostic groups. Low-risk/high-TME patients exhibited significantly superior survival outcomes (p < 0.001), with external validation in the GSE65904 cohort (p = 0.002). Crucially, PTK6 knockdown suppressed tumor progression through increased apoptosis, reduced cell viability, impaired migration, and decreased tumor volume, mediated by Hippo pathway activation.</div></div><div><h3>Conclusions</h3><div>The RS-TME classifier is the first model integrating anoikis resistance and immune microenvironment to predict survival and immunotherapy response. Simultaneously, PTK6 targeting suppresses CM progression via Hippo-mediated anoikis resistance, providing a foundation for personalized treatment strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"966 ","pages":"Article 149686"},"PeriodicalIF":2.4,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-25DOI: 10.1016/j.gene.2025.149699
Jianping Zhang , Yijia Zhao , Tengyan Li , Yu Bai , Yueyuan Lan , Pei Zhong , Wenhui Liu , Binbin Wang
{"title":"A potentially pathogenic KDM5C variant in X-linked high myopia","authors":"Jianping Zhang , Yijia Zhao , Tengyan Li , Yu Bai , Yueyuan Lan , Pei Zhong , Wenhui Liu , Binbin Wang","doi":"10.1016/j.gene.2025.149699","DOIUrl":"10.1016/j.gene.2025.149699","url":null,"abstract":"<div><div>High myopia is a multifactorial ocular disease that demonstrates high genetic susceptibility and significant family aggregation. It has multiple inheritance patterns, including X-linked inheritance; however, few genetic variants associated with X-linked high myopia have been documented. Using a whole exome sequencing approach, we have identified a novel missense variant (c.A3043T: p.Arg1015Trp) in <em>Lysine demethylase 5C</em> (<em>KDM5C</em>) in a Chinese family exhibiting X-linked high myopia. The occurrence of <em>KDM5C</em> c.A3043T in the family was confirmed through Sanger sequencing and the pathogenicity of the variant protein was predicted by bioinformatic analysis. We propose that this report represents a potential correlation of a <em>KDM5C</em> variant with high myopia, which provides a new understanding of X-linked high myopia and expands the <em>KDM5C</em> variant spectrum.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149699"},"PeriodicalIF":2.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenePub Date : 2025-07-25DOI: 10.1016/j.gene.2025.149687
Haibo Du , Xi Huang , Rui Ren , Yixiao Sun , Yanfei Wang
{"title":"TSPEAR S475TfsX79 mutation does not affect auditory function, tooth morphology or hair development in mice","authors":"Haibo Du , Xi Huang , Rui Ren , Yixiao Sun , Yanfei Wang","doi":"10.1016/j.gene.2025.149687","DOIUrl":"10.1016/j.gene.2025.149687","url":null,"abstract":"<div><div>TSPEAR is a member of the EAR (epilepsy-associated repeat) protein family with poorly characterized function. Several lines of evidence suggest that mutations in the human <em>TSPEAR</em> gene are associated with hearing loss or ectodermal dysplasia. Although tooth abnormalities and a reduced capacity for caudal fin regeneration were observed in the <em>Tspeara</em><sup>-/-</sup>;<em>Tspearb</em><sup>-/-</sup> knockout zebrafish model, there have been no reports of the <em>Tspear</em> knockout mouse model to date, which hampers further investigation of its physiological role. Here, we inactivated the <em>Tspear</em> gene in mice using CRISPR/Cas9-mediated genome editing. Intriguingly, stereociliary morphology and auditory function remain unaffected in TSPEAR S475TfsX79 mutant mice. Similarly, tooth morphology and hair development are unaltered in these mutants. Nevertheless, the S475TfsX79 mutation appears to perturb both Notch and Wnt signaling pathways. Specifically, <em>Notch1</em> and several downstream target genes are downregulated, whereas <em>Heyl</em> expression is upregulated in the skin. Additionally, Wnt4 expression is elevated in both the skin and inner ear. In conclusion, our data demonstrate that TSPEAR S475TfsX79 mutation does not compromise auditory function, tooth morphology, or hair development in mice, but TSPEAR may modulate both Notch and Wnt signaling pathways in the mouse.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"965 ","pages":"Article 149687"},"PeriodicalIF":2.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}