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-G point mutation at position 5632 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 congenital heart defects associated with heterotaxy such as vascular sling with isolated left subclavian artery, right aortic arch, muscular vascular septal defect (VSD) and biventricular hypertrophy. A midline liver, left pulmonary isomerism, polysplenia and duplex kidney 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. A T-to-G single point mutation at position 5632 of the cDNA (c.A5632G, NM_010060) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an threonine to alanine amino acid substitution at position 1878 of the encoded protein (p.T1878A).
|Allele Name||Bench to Bassinet Program (B2B/CVDC) mutation 1289, Cecilia Lo|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Dnahc11c.A5632G; Ghost|
|Gene Symbol and Name||Dnah11, dynein, axonemal, heavy chain 11|
|Strain of Origin||C57BL/6J|
|General Note||Summative Diagnosis:|
Cardiovascular phenotype: Congenital heart defects associated with heterotaxy such as vascular sling with isolated left subclavian artery, right aortic arch (RAA), muscular vascular septal defect (VSD), and biventricular hypertrophy
Noncardiovascular phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, midline liver, left pulmonary isomerism, polysplenia, hypoplastic spleen, and malaligned sternal vertebra. Also observed was anophthalmia/microphthalmia, and duplex, cystic, and hydronephrotic kidney with hydroureter
Phenotypic Similarity to Human Syndrome: Heterotaxy, Polysplenia syndrome (left isomerism), Primary Ciliary Dyskinesia (PCD)