C57BL/6J-Daw1^b2b1584Clo/J

Stock number: 018211
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease, Kartagener's Syndrome, Primary Ciliary Dyskinesia, and heterotaxy.

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 mutation 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 here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.

Homozygotes demonstrate laterality defects including situs inversus totalis and heterotaxia with congenital heart disease: dextrocardia, double outlet right ventricle (DORV), possible crisscross heart, and bilateral inferior vena cavae (IVC). Slow and dyskinetic airway ciliary motion are also seen.

Development

This mutation, identified in an ENU screen for recessive cardiovascular development phenotypes, was created and maintained on a C57BL/6J genetic background by the NHLBI Cardiovascular Development Consortium (CvDC), Bench to Bassinet Program.

Allele

Symbol: Daw1^b2b1584Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1584 Cecilia Lo
MGI accession ID: MGI:5431501
Generation method: Chemically induced (ENU)
Marker symbol: Daw1
Marker name: dynein assembly factor with WDR repeat domains 1
Chromosome: 1
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 a T to C substitution at coding nucleotide 197 in exon 3 of the cDNA (c.197T>C, NM_027725). This changes the leucine residue to a proline at position 66 of the encoded protein (p.L66P).
General note: Summative Diagnosis:
Laterality defects including situs inversus totalis and heterotaxia with congenital heart disease: dextrocardia, double outlet right ventricle (DORV), possible crisscross heart, and bilateral inferior vena cavae (IVC), and right aortic arch (RAA)
Noncardiac phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, malaligned sternal vertebra, liver isomerism, left lung isomerism, and hypoplastic spleen/asplenia. Airway cilia were slow and dyskinetic

Phenotypic Similarity to Human Syndrome: Kartagener's Syndrome, Primary Ciliary Dyskinesia, Heterotaxy

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
181	Crisscross Atrioventricular Valves
100	Situs inversus totalis
110	Dextrocardia
190	Heterotaxy Syndrome
2700	Abnormal aortic arch
2720	Right aortic arch
2810	Inferior vena cava anomaly
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
4100	Skeletal, skin, muscle anomaly
4239	Left bronchial isomerism
4447	Hepatic malformation
4771	Asplenia
4851	Kartagener syndrome (siewart syndrome)(primary ciliary dyskinesia)
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality
600	Double outlet right ventricle
606	DORV + AVSD (AV canal)