Protein tyrosine kinase 7 (Ptk7) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida.
Protein tyrosine kinase 7 (Ptk7) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida.
In mice, homozygosity for mutations in the Vangl1 and Vangl2 genes or combined heterozygosity for Vangl1/Vangl2 mutations causes the very severe neural tube defect (NTD) craniorachischisis.
In mice, homozygosity for mutations in the Vangl1 and Vangl2 genes or combined heterozygosity for Vangl1/Vangl2 mutations causes the very severe neural tube defect (NTD) craniorachischisis.
This could be mediated via heparan sulfate residues, as Vangl2(Lp/+) embryos fail to initiate neural tube closure and develop craniorachischisis (usually seen only in Vangl2(Lp/Lp)) when cultured in the presence of chlorate, a sulfation inhibitor.
Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis.
Mouse models indicate that the homozygous disruption of Sec24b, which mediates the ER-to-Golgi transportation of the core PCP gene Vangl2 as a component of the COPII vesicle, will result in craniorachischisis.
The Loop-tail (Lp) mouse that develops craniorachischisis carry missense mutations in the PCP core gene Vangl2, that is the mammalian homolog of the Drosophila Strabismus/Van gogh (Stbm/Vang).
We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
Rare putative mutations in the PCP genes VANGL2, SCRIB, DACT1, and CELSR1 cumulatively contributed to over 20% of cases with craniorachischisis, a rare defect; no contributing variants were found for PRICKLE1 or PTK7.
We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism.
Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida.
Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida.
Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida.