This Drc1 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease.
The Jackson Laboratory cannot guarantee that cryorecovery of G1 sperm from the Bench to Bassinet (B2B) collection will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.
Cecilia Lo, Univ of Pittsburgh School of Medicine
This A to G point mutation at position 2021 of the Drc1 (dynein regulatory complex subunit 1) cDNA was identified in an ENU screen for recessive cardiovascular development phenotypes in Dr. Cecilia Lo's laboratory, NHLBI Cardiovascular Development Consortium (CvDC). It was recovered from G1 sperm and associated with the phenotype described described here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.
Homozygotes demonstrate heterotaxy with complex congenital heart disease such as transposition of the great arteries (TGA), atrioventricular septal defects (AVSD), dual inferior vena cava (IVC), dual hepatic vein, and azygous venous connection. Immotile/dyskinetic airway cilia are also seen.
This ENU-induced mutation was created and maintained on a C57BL/6J genetic background by the NHLBI Cardiovascular Development Consortium (CvDC), Bench to Bassinet Program. An A-to-G single point mutation at position 2021 of the cDNA (c.A2021G, NM_001033460) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a tyrosine to cysteine amino acid substitution at position 674 of the encoded protein (p.Y674C).
|Allele Name||Bench to Bassinet Program (B2B/CVDC), mutation 1654 Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Aardvark; Ccdc164b2b1654Clo|
|Gene Symbol and Name||Drc1, dynein regulatory complex subunit 1|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis:|
Cardiac phenotype: Cardiovascular phenotype: Heterotaxy with complex congenital heart disease such as dextrocardia/levocardia, transposition of the great arteries (TGA), ventricular (VSD) and atrioventricular septal defects (AVSD), dual inferior vena cava (IVC), interrupted aortic arch type B (IAA), dual hepatic vein, and azygous venous connection. Also observed are mutants with situs inversus totalis without congenital heart defects
Noncardiac phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, inverted liver lobation, left lung isomerism, malaligned sternal vertebra, and apslenia. Also observed were micrognathia and immotile/dyskinetic airway cilia