C57BL/6J-Dnah11^b2b1727Clo/J

Stock number: 018237
Research areas: Cardiovascular Research, Developmental Biology Research, Endocrine Deficiency 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.

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 in the Dnah11 (dynein, axonemal, heavy chain 11) gene 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 complex congenital heart disease associated with heterotaxy such as double outlet right ventricle (DORV) with subaortic ventricular septal defect, atrioventricular septal defect (AVSD), and hypoplastic/abnormal spleen. Immotile/hyperkinetic/dyskinetic respiratory airway cilia and hydronephrosis are also seen.

Development

This mutation in the Dnah11 gene, 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: Dnah11^b2b1727Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 1727, Cecilia Lo
MGI accession ID: MGI:5437727
Generation method: Chemically induced (ENU)
Marker symbol: Dnah11
Marker name: dynein, axonemal, heavy chain 11
Chromosome: 12
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. The causitive molecular lesion for the cardiovascular phenotypes is a T to C substitution in the +2 position after coding nucleotide 1137 of the cDNA (c.1137+2T>C, NM_010060) in intron 6 of the gene. This changes the splice donor site from G-GT to G-GC (which is assumed to be less efficient).
General note: Summative Diagnosis:
Cardiovascular phenotype: Complex congenital heart disease associated with heterotaxy such as levocardia/dextrocardia, double outlet right ventricle (DORV) with subaortic ventricular septal defect (VSD), atrioventricular septal defect (AVSD), right aortic arch (RAA)
Noncardiovascular phenotype: Situs inversus totalis, as well as abnormal thoracic and abdominal organ situs anomalies, such as hypoplastic/abnormal spleen. Also observed was immotile/hyperkinetic/dyskinetic respiratory airway cilia and hydronephrosis

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 Code ID	Code Description
0100	Situs inversus totalis
0110	Dextrocardia
0190	Heterotaxy Syndrome
0600	Double outlet right ventricle
0602	DORV, ventricular defect committed to aorta
1100	Atrioventricular canal (endocardial cushion defect)
1300	Ventricular septal defect
2700	Abnormal aortic arch
2720	Right aortic arch
3804	Congenital heart disease
3816	Abdominal situs inversus
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3950	{S,D,D}
3974	{I,L,I}
4502	Hydronephrosis
4851	Kartagener syndrome (siewart syndrome)(primary ciliary dyskinesia)
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality