Mtnr1a-KO Mouse

MTNR1A, encoding melatonin receptor 1A, is a key player in mediating the effects of melatonin. Melatonin is involved in regulating the mammalian circadian rhythm, glucose homeostasis, and reproductive functions. MTNR1A is expressed in various tissues and cells, such as pancreatic beta cells, renal tubular cells, and cells in the hypothalamus-pituitary-gonadal axis, and is thus associated with multiple physiological pathways [1-4, 7].

In renal tubular cells, cytoplasmic heterogeneous nuclear ribonucleoprotein L (hnRNPL) post-transcriptionally upregulates MTNR1A RNA by stabilizing its transcript through CA-repeat elements, protecting it from degradation by exosome component 10 protein. MTNR1A shows a diurnal rhythm in mouse kidneys [1]. In Italian families, certain MTNR1A gene variants were significantly linked to and/or associated with type 2 diabetes, suggesting it as a novel risk gene [2]. In different Mediterranean sheep breeds, MTNR1A gene polymorphisms affected reproductive performance, including fertility and the duration from ram placement to lambing [3,6]. In Tibetan sheep, the expression of MTNR1A in the hypothalamus-pituitary-gonadal axis varied during the estrous cycle, potentially affected by steroid hormone secretion [4]. In buffalo, the expression of MTNR1A gene transcript decreased with increasing follicle size and intrafollicular melatonin concentration, indicating a role in folliculogenesis and ovulation [5].

In conclusion, MTNR1A is crucial for various physiological functions including circadian rhythm, glucose metabolism, and reproduction. Studies on MTNR1A in different animal models have provided insights into its role in diseases like type 2 diabetes and its impact on reproductive processes in sheep and buffalo. These findings enhance our understanding of the biological functions of MTNR1A and its potential implications in human health and animal production.

References:

1. Huang, Yen-Sung, Lu, Kuo-Cheng, Chao, Hsu-Wen, Sytwu, Huey-Kang, Wu, Chia-Chao. 2020. The MTNR1A mRNA is stabilized by the cytoplasmic hnRNPL in renal tubular cells. In Journal of cellular physiology, 236, 2023-2035. doi:10.1002/jcp.29988. https://pubmed.ncbi.nlm.nih.gov/32730662/

2. Amin, M, Gragnoli, C. . Melatonin receptor 1A (MTNR1A) gene linkage and association to type 2 diabetes in Italian families. In European review for medical and pharmacological sciences, 27, 4688-4692. doi:10.26355/eurrev_202305_32480. https://pubmed.ncbi.nlm.nih.gov/37259752/

3. Pulinas, L, Starič, J, Cosso, G, Carcangiu, V, Luridiana, S. 2021. MTNR1A gene polymorphisms and reproductive recovery after seasonal anoestrus in different Mediterranean sheep breeds. In Animal reproduction science, 236, 106905. doi:10.1016/j.anireprosci.2021.106905. https://pubmed.ncbi.nlm.nih.gov/34922186/

4. Yang, Dapeng, He, Yuqin, Yuan, Ligang, Zhou, Kairen, Bao, Yingying. 2022. Expression and distribution of MTNR1A in the hypothalamus-pituitary-gonadal axis of Tibetan sheep during the estrous cycle. In Gene, 839, 146731. doi:10.1016/j.gene.2022.146731. https://pubmed.ncbi.nlm.nih.gov/35835405/

5. Soni, N, Pandey, A K, Kumar, A, Kumar, V, Singh, V. 2019. Expression of MTNR1A, steroid (ERα, ERβ, and PR) receptor gene transcripts, and the concentration of melatonin and steroid hormones in the ovarian follicles of buffalo. In Domestic animal endocrinology, 72, 106371. doi:10.1016/j.domaniend.2019.06.003. https://pubmed.ncbi.nlm.nih.gov/31421986/

6. Arjoune, Asma, Alsaleh, Abrar B, Messaoudi, Safia A, Haddad, Brahim, Sirard, Marc-André. 2023. Analysis of MTNR1A Genetic Polymorphisms and Their Association with the Reproductive Performance Parameters in Two Mediterranean Sheep Breeds. In Animals : an open access journal from MDPI, 13, . doi:10.3390/ani13030448. https://pubmed.ncbi.nlm.nih.gov/36766337/