Overexpression of the KCTD13 gene in zebrafish resulted in induction of the microcephaly phenotype associated with 16p11.2 duplications, whereas suppression of KCTD13 expression resulted in the macrocephaly phenotype associated with 16p11.2 deletions (Golzio et al., 2012). An autistic proband with a de novo deletion including exons 3-5 of the KCTD13 gene was also identified in this report.
Molecular Function
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for synaptic transmission (PMID 19782033). The BCR(KCTD13) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome (PMID 19782033) Degradation of RHOA regulates the actin cytoskeleton and promotes synaptic transmission.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant.
Overexpression of BBS7 rescues head size and neuroanatomical defects of kctd13 morphants, whereas suppression or overexpression of CEP290 rescues phenotypes induced by KCTD13 under- or overexpression, respectively. Lack of kctd13 on a mitf1a null background results in no increase in head size or cell proliferation but increases RhoA protein expression in the brain.
References
Type
Title
Author, Year
Primary
KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant.
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Human wild type mRNA was cloned into the pCS2 vector and transcribed in vitro and injected into wildtype zebrafish embryos at the 1-2 cell stage. Capped mRNA was generated and injected zebrafish embryos with equimolar pairwise cocktail combinations at two dosages of 25 pg and 50 pg; these commonly used ranges were selected because they represent >0.250.5% of total polyA+ mRNA in a zebrafish embryo and are thus likely to achieve significant overexpression above the baseline of any single transcript.
Allele Type: Overexpression
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 22596160
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Wildtype Zebrafish embryos were injected with splice blocking morpholios against Kctd13 at the 1-to 2-cell stage. Control MO was the scrambled nucleotide sequence from Gene Tools, LLC.
Allele Type: Loss of Function
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 22596160
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
100 pg wildtype CEP290 human transcript was injected into wild-type zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 25937446
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
10ng splice-blocking MOs against kctd13 was injected into wild-type zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Loss of Function
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 25937446
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
100 pg wildtype KCTD13 human transcript was injected into wild-type zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 25937446
Model Type:
Genetic
Model Genotype:
Wild type
Mutation:
Kctd13 human transcript was over-expressed by injection into wildtype zebrafish embryos at the 1- to 2-cell stage.
Allele Type: Overexpression
Strain of Origin: Genetic Background: ES Cell Line: Mutant ES Cell Line: Model Source: 28965845
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The kctd13 mutant, ZFIN mutant line kctd13^a160, was generated by simultaneous injection of four guide RNAs (gRNAs) and approximately 0.5microliter of 50 micromolar Cas9 protein into embryos from a nacre (mitfa/) line crossed to an EK line. The out-of-frame mutant, a 46-bp insertion at the first gRNA target and 37-bp deletion between the second and third gRNA targets was identified and sequenced.
Allele Type: Loss of function
Strain of Origin: EK
Genetic Background: EK
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 29088697
Description: Injection of cep290 transcript alone increased ectopic HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Injection of cep290 mRNA alone reduced bilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Cep290 transcript injection increased unilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Morphants show reduced bilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Morphants show increased unilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Total number of neurons was increased in kctd13 morphants compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Suppression of kctd13 led to an increased number of newborn neurons compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Suppression of kctd13 led to the ectopic expression of HuC/D concomitant with an increased number of newborn neurons and macrocephaly
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Kctd13 mRNA injection increased unilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: Injection of kctd13 transcript reduced HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
Description: KCTD13 mRNA injection shows reduced bilateral HuC/D expression compared to controls.
Exp Paradigm: Injected embryos were stained with HuC/D antibody. Anti-HuC/D is a marker for post- mitotic neurons, i.e., cells positive for HuC and HuD (also known as ELAVL3 and ELAVL4).
