This Dnai1 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease and other developmental defects.
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
A T-to-A mutation in Dnai1 (dynein, axonemal, intermediate chain 1) 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 cardiovascular defects that involve situs inversus totalis and heterotaxy with congenital heart disease. Immotile tracheal airway cilia are also seen. This strain may be used as a model of Kartagener's Syndrome, Primary Ciliary Dyskinesia and heterotaxy.
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 T-to-C single point mutation at position 1565 of the cDNA (c.T1565C, NM_175138) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a isoleucine to threonine amino acid substitution at position 522 of the encoded protein (p.I522T).
|Allele Name||Bench to Bassinet Program (B2B/CVDC), mutation 1526 Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||Dnai1, dynein axonemal intermediate chain 1|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis:|
Cardiovascular phenotype: Situs inversus totalis and heterotaxy with complex congenital heart disease such as dextrocardia, dual inferior vena cava (IVC), aortic arch stenosis, and biventricular hypertrophy
Noncardiovascular phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, malaligned sternal vertebra, hypoplastic spleen, liver isomerism, and left lung isomerism. Also observed were micrognathia, short snout, and immotile tracheal airway cilia