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C57BL/6NCya-Klhl15em1/Cya
Common Name:
Klhl15-KO
Product ID:
S-KO-06868
Background:
C57BL/6NCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Klhl15-KO
Strain ID
KOCMP-236904-Klhl15-B6N-VA
Gene Name
Klhl15
Product ID
S-KO-06868
Gene Alias
6330500C13Rik
Background
C57BL/6NCya
NCBI ID
236904
Modification
Conventional knockout
Chromosome
X
Phenotype
MGI:1923400
Document
Click here to download >>
Application
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Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6NCya-Klhl15em1/Cya mice (Catalog S-KO-06868) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000113916
NCBI RefSeq
NM_001039061
Target Region
Exon 2
Size of Effective Region
~0.7 kb
Detailed Document
Click here to download >>
Overview of Gene Research
Klhl15, a substrate adaptor for cullin3-containing E3 ubiquitin ligases, is located on chromosome Xp22.11. It plays a crucial role in protein turnover, which is essential for proper cellular function. It is involved in pathways such as DNA double-strand break repair [1,3] and neuronal development [5]. Its function in protein turnover makes it important for maintaining cellular homeostasis and normal biological development. Genetic models can be valuable in studying Klhl15's specific functions in vivo.

In DNA-end resection, Klhl15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A conserved tripeptide motif (FRY) in CtIP is essential for Klhl15-binding. Overexpression of Klhl15 attenuates DNA-end resection, while its absence or expression of a CtIP-FRY mutant amplifies it, affecting the balance between homologous recombination and non-homologous end-joining [1]. In neuronal dendritogenesis, Klhl15 degrades doublecortin proteins. A FRY tripeptide at the C-terminal edge of the second DCX domain is necessary for Klhl15-mediated ubiquitination and subsequent proteasomal degradation of doublecortin and doublecortin-like kinase 1 and 2. Silencing endogenous Klhl15 stabilizes these proteins [5]. Mutations in Klhl15 are related to X-linked intellectual disability. A patient with a novel nonsense variant in Klhl15 presented with impaired intelligence, short stature, frequent hypoglycemia, and periodic fever [2]. Another patient with a novel variant showed global developmental delay, coarse facial features, etc. [4].

In conclusion, Klhl15 is crucial for protein turnover in processes like DNA repair and neuronal development. Model-based research, especially studies on its loss-of-function, has revealed its role in X-linked intellectual disability. Understanding Klhl15's functions can provide insights into the mechanisms of DNA repair and neurodevelopmental disorders [1,2,4,5].

References:

1. Ferretti, Lorenza P, Himmels, Sarah-Felicitas, Trenner, Anika, Porro, Antonio, Sartori, Alessandro A. 2016. Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection. In Nature communications, 7, 12628. doi:10.1038/ncomms12628. https://pubmed.ncbi.nlm.nih.gov/27561354/

2. Kido, Jun, Egami, Kimiyasu, Misumi, Yohei, Ueda, Mitsuharu, Nakamura, Kimitoshi. 2023. X-linked intellectual disability related to a novel variant of KLHL15. In Human genome variation, 10, 21. doi:10.1038/s41439-023-00248-7. https://pubmed.ncbi.nlm.nih.gov/37452054/

3. Wu, Wei, Fan, Zhenzhen, Fu, Hui, Tang, Tie-Shan, Guo, Caixia. 2024. VGLL3 modulates chemosensitivity through promoting DNA double-strand break repair. In Science advances, 10, eadr2643. doi:10.1126/sciadv.adr2643. https://pubmed.ncbi.nlm.nih.gov/39383226/

4. Caswell, Richard C, Baptista, Julia, Cairns, Lauren M, Wilson, Kate, Stewart, Helen. 2023. Clinical findings and structural analysis involving a patient with a novel KLHL15 variant. In European journal of medical genetics, 66, 104768. doi:10.1016/j.ejmg.2023.104768. https://pubmed.ncbi.nlm.nih.gov/37059329/

5. Song, Jianing, Merrill, Ronald A, Usachev, Andrew Y, Strack, Stefan. 2020. The X-linked intellectual disability gene product and E3 ubiquitin ligase KLHL15 degrades doublecortin proteins to constrain neuronal dendritogenesis. In The Journal of biological chemistry, 296, 100082. doi:10.1074/jbc.RA120.016210. https://pubmed.ncbi.nlm.nih.gov/33199366/

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
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