Cartpt-KO Mouse

Cartpt, encoding the cocaine-and amphetamine-regulated transcript prepropeptide, is involved in multiple biological processes. It plays roles in reward and feeding behavior, with functional characteristics similar to an endogenous psychostimulant [7]. It also participates in various physiological and pathological regulations, including those related to metabolism, cardiovascular and skeletal development, and ovarian follicular development [3,4,5,6,2].

In male human thoracic aortic aneurysm (TAA) samples, a spatially distinct CARTPT-expressing smooth muscle cell (SMC) subtype was identified. Functional studies suggest that human CART, the product of Cartpt, promotes the osteochondrogenic switch of aortic SMCs, potentially leading to medial calcification of the thoracic aorta [1]. In preosteoblast-specific Atrx conditional knockout mice, Atrx deletion led to high levels of Cartpt expression in osteolineage cells. Mechanistically, ATRX suppresses Cartpt transcription by binding to the promoter. Cartpt silencing in these cells rescued the molecular phenotype by increasing the Rankl/Opg expression ratio, indicating Cartpt's role in skeletal development [2].

In summary, Cartpt is involved in diverse biological functions including reward processing, cardiovascular and skeletal development, and ovarian follicular regulation. Studies using gene knockout or conditional knockout mouse models, like the Atrx conditional knockout mouse model, have provided insights into Cartpt's role in skeletal development and its potential implications in diseases such as thoracic aortic aneurysms. These findings contribute to understanding the molecular mechanisms underlying these biological processes and diseases [1,2].

References:

1. Mizrak, Dogukan, Zhao, Yang, Feng, Hao, Yang, Bo, Chen, Y Eugene. 2023. Single-Molecule Spatial Transcriptomics of Human Thoracic Aortic Aneurysms Uncovers Calcification-Related CARTPT-Expressing Smooth Muscle Cells. In Arteriosclerosis, thrombosis, and vascular biology, 43, 2285-2297. doi:10.1161/ATVBAHA.123.319329. https://pubmed.ncbi.nlm.nih.gov/37823268/

2. Chen, Yi-Ting, Jiang, Ming-Ming, Leynes, Carolina, Bae, Yangjin, Lee, Brendan. 2025. ATRX silences Cartpt expression in osteoblastic cells during skeletal development. In The Journal of clinical investigation, 135, . doi:10.1172/JCI163587. https://pubmed.ncbi.nlm.nih.gov/39744954/

3. Smith, G W, Sen, A, Folger, J K, Ireland, J J. . Putative role of cocaine- and amphetamine-regulated transcript (CARTPT) in dominant follicle selection in cattle. In Society of Reproduction and Fertility supplement, 67, 105-17. doi:. https://pubmed.ncbi.nlm.nih.gov/21755666/

4. Mahmoudi-Nezhad, Mahsa, Farhangi, Mahdieh Abbasalizad, Kahroba, Houman. 2020. Cocaine and amphetamine-regulated transcript prepropeptide gene (CARTPT) polymorphism interacts with Diet Quality Index-International (DQI-I) and Healthy Eating Index (HEI) to affect hypothalamic hormones and cardio-metabolic risk factors among obese individuals. In Journal of translational medicine, 18, 16. doi:10.1186/s12967-020-02208-z. https://pubmed.ncbi.nlm.nih.gov/31918705/

5. Khodarahmi, Mahdieh, Siri, Goli, Erahimzadeh, Farnoosh, Farhangi, Mahdieh Abbasalizad, Shanehbandi, Dariush. 2022. Dietary glycemic index and glycemic load mediate the effect of CARTPT rs2239670 gene polymorphism on metabolic syndrome and metabolic risk factors among adults with obesity. In BMC endocrine disorders, 22, 288. doi:10.1186/s12902-022-01188-z. https://pubmed.ncbi.nlm.nih.gov/36404325/

6. Mahmoudinezhad, Mahsa, Abbasalizad-Farhangi, Mahdieh, Kahroba, Houman. 2021. Hypothalamic-pituitary hormones will be affected by the interaction between 5q13-14-rs2239670 (CARTPT) gene variants and diet in different obesity phenotypes. In BMC research notes, 14, 443. doi:10.1186/s13104-021-05857-5. https://pubmed.ncbi.nlm.nih.gov/34876220/

7. Lohoff, Falk W, Bloch, Paul J, Weller, Andrew E, O'Brien, Charles P, Berrettini, Wade H. 2008. Genetic variants in the cocaine- and amphetamine-regulated transcript gene (CARTPT) and cocaine dependence. In Neuroscience letters, 440, 280-3. doi:10.1016/j.neulet.2008.05.073. https://pubmed.ncbi.nlm.nih.gov/18572320/