C57BL/6JCya-Glmnem1flox/Cya
Common Name:
Glmn-flox
Product ID:
S-CKO-18386
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Glmn-flox
Strain ID
CKOCMP-170823-Glmn-B6J-VB
Gene Name
Product ID
S-CKO-18386
Gene Alias
9330160J16Rik; Fap48; Fap68
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
5
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Glmnem1flox/Cya mice (Catalog S-CKO-18386) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000078021
NCBI RefSeq
NM_133248
Target Region
Exon 6~7
Size of Effective Region
~2.9 kb
Detailed Document
Overview of Gene Research
Glmn, encoding glomulin, is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex [5]. It has been associated with multiple biological processes and disease conditions. Mutations in Glmn can lead to glomuvenous malformations (GVMs), which present as blue-pink lesions on the skin or mucosal surfaces, often causing pain, unsightly appearance, and potential bleeding [1,4,6,8]. Glmn also binds to FK506-binding proteins (FKBP), specifically FKBP12.6 and FKBP51, and its interaction with FKBP51 can be blocked by FKBP ligands, suggesting FKBP inhibition as a potential pharmacological approach to regulate Glmn-controlled processes [5].
Loss-of-function variants in GLMN have been associated with generalized skin hyperpigmentation, with or without glomuvenous malformation. In five unrelated families, five different loss-of-function variants in GLMN were identified. In these cases, although the number of melanocytes remained unchanged in hyperpigmented skin lesions, there was an increased number of melanosomes. Knockdown of GLMN in human MNT-1 cells led to a higher melanin concentration, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6K, indicating a role of Glmn in human skin melanogenesis [2]. Rare germline variants in GLMN were identified from patients with Blue Rubber Bleb Nevus Syndrome (BRBN), and these variants led to increased phosphorylation of mTOR-Ser-2448 in HUVECs, suggesting that GLMN might contribute to the pathogenesis of BRBN through abnormal mTOR signaling [3]. Shigella can hijack Glmn by delivering the IpaH7.8 E3 ubiquitin ligase, which ubiquitinates and degrades Glmn, leading to inflammasome activation and pyroptotic cell death of macrophages. Glmn specifically binds to cIAP1 and cIAP2, reducing their E3 ligase activity and inflammasome-mediated death of macrophages, indicating that Glmn is a negative regulator of cIAP-mediated inflammasome activation [7].
In conclusion, Glmn plays essential roles in vascular morphogenesis, skin melanogenesis, and inflammasome regulation. Loss-of-function models, including knockdown experiments in cell lines and identification of loss-of-function variants in patients, have revealed its functions in diseases such as glomuvenous malformations, skin hyperpigmentation, BRBN, and Shigella-induced inflammation. Understanding Glmn functions provides potential therapeutic targets for these associated diseases.
References:
1. McMahon, Mollie Helena, Tahir, Nasim, Balasubramanian, Meena. 2022. GLMN causing vascular malformations: the clinical and genetic differentiation of cutaneous venous malformations. In BMJ case reports, 15, . doi:10.1136/bcr-2021-246114. https://pubmed.ncbi.nlm.nih.gov/35732373/
2. Jiang, Xingyuan, Yang, Chao, Wang, Zhaoyang, Wang, Huijun, Lin, Zhimiao. . Loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. In The British journal of dermatology, 191, 107-116. doi:10.1093/bjd/ljae108. https://pubmed.ncbi.nlm.nih.gov/38489583/
3. Yin, Jie, Qin, Zhongping, Wu, Kai, Hu, Landian, Kong, Xiangyin. . Rare Germline GLMN Variants Identified from Blue Rubber Bleb Nevus Syndrome Might Impact mTOR Signaling. In Combinatorial chemistry & high throughput screening, 22, 675-682. doi:10.2174/1386207322666191203110042. https://pubmed.ncbi.nlm.nih.gov/31793416/
4. Henning, J Scott, Kovich, Olympia I, Schaffer, Julie V. 2007. Glomuvenous malformations. In Dermatology online journal, 13, 17. doi:. https://pubmed.ncbi.nlm.nih.gov/17511950/
5. Hähle, Andreas, Geiger, Thomas M, Merz, Stephanie, Kolos, Jürgen, Hausch, Felix. 2019. FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin. In PloS one, 14, e0221926. doi:10.1371/journal.pone.0221926. https://pubmed.ncbi.nlm.nih.gov/31490997/
6. Skowronek, Dariush, Hebebrand, Moritz, Erber, Ramona, Felbor, Ute, Rath, Matthias. . Identification and characterization of a GLMN splice site variant in a family with glomuvenous malformations. In European journal of dermatology : EJD, 30, 179-181. doi:10.1684/ejd.2020.3716. https://pubmed.ncbi.nlm.nih.gov/32538359/
7. Suzuki, Shiho, Suzuki, Toshihiko, Mimuro, Hitomi, Mizushima, Tsunehiro, Sasakawa, Chihiro. 2017. Shigella hijacks the glomulin-cIAPs-inflammasome axis to promote inflammation. In EMBO reports, 19, 89-101. doi:10.15252/embr.201643841. https://pubmed.ncbi.nlm.nih.gov/29191979/
8. Ramessur, Ravi, Fadhli, Tamara, Tripathi, Bharati, Sandhu, Daisy, Batta, Kapila. . Glomovenous malformation secondary to a heterozygous nonsense variant in GLMN: a clinical mimicker of blue rubber bleb naevus syndrome. In Clinical and experimental dermatology, 49, 108-110. doi:10.1093/ced/llad302. https://pubmed.ncbi.nlm.nih.gov/37655781/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen