This Dnah11 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.
Cecilia Lo, Univ of Pittsburgh School of Medicine
Two thymine (T) T bases inserted at position 6489 of the Dnah11 (dynein, axonemal, heavy chain 11) cDNA were 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 dextrocardia associated with heterotaxy, duplicated inferior vena cava (IVC), and inverted hemizygous connection. Gut malrotation, hypoplastic spleen, and possible biliary obstruction. Dyskinetic and hyperkinetic airway cilia are also seen.
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. Two thymine (T) T bases inserted at position 6489 of the cDNA (c.6489+2T, NM_010060) were discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a frameshift at position 2163 of the encoded protein (p.K2163fs*).
|Allele Name||Bench to Bassinet Program (B2B/CVDC) mutation 1775, Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Blindfold; Dnahc11c.6489+2T|
|Gene Symbol and Name||Dnah11, dynein, axonemal, heavy chain 11|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis:|
Cardiovascular phenotype: Dextrocardia associated with heterotaxy, duplicated IVC, inverted hemiazygous connection, double outlet right ventricle (DORV), subaortic ventricular septal defect (VSD)
Noncardiovascular phenotype: Situs inversus totalis, as well as heterotaxy with abnormal thoracic and abdominal organ situs anomalies, such as different combinations with dextrogastria, malaligned sternal vertebra and hypoplastic spleen. Also observed were gut malrotation, possible biliary obstruction, as well as dyskinetic and hyperkinetic airway cilia