This Dnah11 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 A-to-T point mutation at position 10369 of the Dnah11 (dynein, axonemal, heavy chain 11) 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 situs inversus totalis and heterodoxy with congenital heart disease including transposition of the great arteries (d-TGA) with ventricular septal defects (VSD). Airway cilia show a wide range of motion defects including immotility, hyperkinetic beat, dyskinetic and slow cilia motility.
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-T single point mutation at position 10369 of the Dnah11 cDNA (c.A10369T, NM_010060) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an isoleucine to a phenylalanine substitution at position 3457 of the encoded protein (p.I3457F).
|Allele Name||Bench to Bassinet Program (B2B/CVDC) mutation 1279, Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||Dnah11, dynein, axonemal, heavy chain 11|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis:|
Cardiovascular phenotype: Situs inversus totalis and heterotaxy presenting with spectrum of congenital heart disease, including dextrocardia, transposition of the great arteries (d-TGA), double outlet right ventricle (DORV) with atrioventricular (AVSD) ventricular septal defects (VSD), mitral valve atresia, and ventricular non-compaction
Noncardiovascular phenotype: Situs inversus totalis and abnormal thoracic and abdominal organ situs anomalies associated with heterotaxy, such as dextrogastria, hypoplastic spleen, left lung isomerism, and malaligned sternal vertebra. Also observed was micrognathia and airway cilia showing a wide range of motion defects including immotility, hyperkinetic beat, dyskinetic and slow cilia motility.