This Dnah5 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of heterotaxy and 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 c.13169T>C Dnahc5 (dynein, axonemal, heavy chain 5) point 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 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 heterotaxy. Congenital heart disease (CHD) is marked by double outlet right ventricle (DORV), atrioventricular septal defects (AVSD), superior-inferior ventricles, and likely other structural heart defects.
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. A c.13169T>C mutation in the Dnah5 gene was discovered through whole exome, high throughput sequencing (RefSeq NM_133365). This mutation is predicted to result in a lysine to proline substitution at codon 4390 (p.Lys4390>Pro) of the expressed protein.
|Allele Name||Bench to Bassinet Program (B2B/CVDC), mutation 002 Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Scar; Scaramanga|
|Gene Symbol and Name||Dnah5, dynein, axonemal, heavy chain 5|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis|
Cardiovascular defects:Situs inversus totalis and heterotaxy with congenital heart disease such as dextrocardia, double outlet right ventricle (DORV), transposition of the great arteries (TGA), ventricular (VSD), atrial (ASD), and atrioventricular septal defect (AVSD), and superior-inferior ventricles.
Non-cardiovascular defects: Abnormal thoracic and abdominal organ situs anomalies, such as malalignment of sternal vertebrae, right pulmonary isomerism, hypoplastic spleen, as well as inverted liver and lung. Also observed were kidney defects such as duplex, cystic, and hydronephrotic. Tracheal airway cilia were immotile.