C57BL/6J-Drc1^b2b1654Clo/J

Stock number: 018224
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

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.

Detailed description

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.

Development

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

Symbol: Drc1^b2b1654Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1654 Cecilia Lo
MGI accession ID: MGI:5438062
Generation method: Chemically induced (ENU)
Synonyms: Aardvark; Ccdc164^b2b1654Clo
Marker symbol: Drc1
Marker name: dynein regulatory complex subunit 1
Marker synonyms: b2b1654Clo; C2orf39; CCDC164; CILD21; Gm1060; LOC381738; SPGF80
Chromosome: 5
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. The molecular lesion is an A to G substitution at coding nucleotide 2021 in exon 15 of the cDNA (c.2021A>G, NM_001033460). this changes the tyrosine residue to cysteine at position 674 of the encoded protein (p.Y674C).
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

Fyler Codes
The Fyler code developed by The Boston Children's Heart Foundation in Boston Children's Hospital provides a hierarchical clinical diagnosis of congenital cardiovascular defects and other disorders. These codes are used to delineate pathology in the mutant mouse models that parallel human disease and can be cross referenced to the International Pediatric and Congenital Cardiac Code (IPCCC) (http://www.ipccc.net/).

Fyler Codes	Code Description
110	Dextrocardia
800	L-loop transpostion of the great arteries
100	Situs inversus totalis
1250	Interrupted aortic arch
1252	Interrupted aortic arch type b
1300	Ventricular septal defect
190	Heterotaxy Syndrome
2700	Abnormal aortic arch
2810	Inferior vena cava anomaly
3816	Abdominal situs inversus
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3974	{I,L,I}
4100	Skeletal, skin, muscle anomaly
4163	Micrognathia
4239	Left bronchial isomerism
4771	Asplenia
4851	Kartagener syndrome (siewart syndrome)(primary ciliary dyskinesia)
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality