Erlec1-KO Mouse

Erlec1, also known as endoplasmic reticulum lectin 1, is likely involved in the endoplasmic reticulum-associated degradation (ERAD) pathway as SEL1L recruits it to form a functional HRD1 ERAD complex [9]. It may also respond to endoplasmic reticulum stress as its gene expression can be induced by ER stressors in certain cell lines [7].

In Class III malocclusion, a rare heterozygous variant in Erlec1 was identified. This gene is highly expressed in mouse jaw osteoblasts and inhibits osteoblast proliferation, with the identified variant significantly enhancing this inhibitory effect. Also, the proper level of Erlec1 expression is crucial for proper osteogenic differentiation, suggesting it plays a role in the genetic basis of Class III malocclusion [1].

In a Mendelian randomization study, a 1 standard deviation increase in the ERLEC1-201-to-ERLEC1-202 splice variant ratio was associated with a reduced risk of schizophrenia [2]. Additionally, in a study exploring the gut-bladder axis, Erlec1 was identified as one of the hub genes differentially expressed between interstitial cystitis patients and healthy individuals, representing a potential therapeutic target [3]. In the context of genetic overlap between schizophrenia and constipation, Erlec1 was among the mapped genes [4]. A Mendelian randomization analysis also found that ERLEC1 in plasma was positively associated with intelligence and cognitive performance [5].

In prostate cancer, FBXL4 potentially controls cancer metastasis through regulation of ERLEC1 levels [6]. In a mouse model of cancer-related cognitive impairment, Erlec1 expression was upregulated in the brains of mice treated with concurrent hindlimb radiation and doxorubicin compared to control brains [8].

In summary, Erlec1 is involved in multiple biological processes and disease conditions. Its role in osteoblast proliferation and differentiation is significant for Class III malocclusion. Its associations with schizophrenia, interstitial cystitis, and cognitive performance also highlight its importance in neurological-related conditions. Additionally, its potential link to cancer metastasis in prostate cancer and its expression changes in a cancer-treatment-related cognitive impairment model further emphasize its diverse functions in disease. The study of Erlec1 using various research models helps to better understand its functions in these disease areas.

References:

1. Rao, Chunbao, Guan, Biyang, Luo, Dong, Zhong, Baimao, Lu, Xiaomei. 2020. Identification of pathogenic variants of ERLEC1 in individuals with Class III malocclusion by exome sequencing. In Human mutation, 41, 1435-1446. doi:10.1002/humu.24054. https://pubmed.ncbi.nlm.nih.gov/32442352/

2. Lu, Tianyuan, Forgetta, Vincenzo, Greenwood, Celia M T, Zhou, Sirui, Richards, J Brent. 2022. Circulating Proteins Influencing Psychiatric Disease: A Mendelian Randomization Study. In Biological psychiatry, 93, 82-91. doi:10.1016/j.biopsych.2022.08.015. https://pubmed.ncbi.nlm.nih.gov/36280454/

3. Fu, Chaowei, Zhao, Yu, Zhou, Xiang, Liu, Fengping, Feng, Ninghan. 2024. Gut microbiota and interstitial cystitis: exploring the gut-bladder axis through mendelian randomization, biological annotation and bulk RNA sequencing. In Frontiers in immunology, 15, 1395580. doi:10.3389/fimmu.2024.1395580. https://pubmed.ncbi.nlm.nih.gov/39399486/

4. Luo, Qinghua, An, Mingwei, Wu, Yunxiang, Zhang, Leichang, Wang, Chen. 2025. Genetic overlap between schizophrenia and constipation: insights from a genome-wide association study in a European population. In Annals of general psychiatry, 24, 11. doi:10.1186/s12991-025-00551-3. https://pubmed.ncbi.nlm.nih.gov/40033405/

5. Zhao, Wei, Zhang, Xinyu, Li, Feng, Yan, Cheng. 2024. Mendelian Randomization Estimates the Effects of Plasma and Cerebrospinal Fluid Proteins on Intelligence, Fluid Intelligence Score, and Cognitive Performance. In Molecular neurobiology, 62, 4922-4934. doi:10.1007/s12035-024-04542-5. https://pubmed.ncbi.nlm.nih.gov/39495227/

6. Stankiewicz, Elzbieta, Mao, Xueying, Mangham, D Chas, Berney, Daniel M, Lu, Yong-Jie. 2017. Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer. In Scientific reports, 7, 5124. doi:10.1038/s41598-017-05209-z. https://pubmed.ncbi.nlm.nih.gov/28698647/

7. Misiewicz, Michael, Déry, Marc-André, Foveau, Bénédicte, Ruths, Derek, LeBlanc, Andréa C. 2013. Identification of a novel endoplasmic reticulum stress response element regulated by XBP1. In The Journal of biological chemistry, 288, 20378-91. doi:10.1074/jbc.M113.457242. https://pubmed.ncbi.nlm.nih.gov/23737521/

8. Demos-Davies, Kimberly, Lawrence, Jessica, Ferreira, Clara, Seelig, Davis. 2023. The Distant Molecular Effects on the Brain by Cancer Treatment. In Brain sciences, 14, . doi:10.3390/brainsci14010022. https://pubmed.ncbi.nlm.nih.gov/38248237/

9. Lin, Liangguang Leo, Wei, Xiaoqiong, Wang, Huilun Helen, Sun, Shengyi, Qi, Ling. 2023. SEL1L-HRD1 interaction is prerequisite for the formation of a functional HRD1 ERAD complex. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.04.13.536796. https://pubmed.ncbi.nlm.nih.gov/37333389/