This Ccdc39 mutation and at least one other undefined mutation were 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
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) | b2b2025Clo | Mutant line 2025 |
Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) | Ccdc39 | coiled-coil domain containing 39 |
Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) | b2b2025.2Clo | Mutant line 2025.2 |
This mutant strain, carrying at least two mutations, 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.
Two mutant phenotypes are observed. In the first, associated with the Ccdc39 gene, homozygotes demonstrate cardiovascular defects that involve heterotaxy presenting with dextrocardia/dextroversion and a spectrum of complex congenital heart disease such as superior-inferior ventricles, overriding aorta/double outlet right ventricle (DORV), DORV Taussig Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), perimembranous and muscular ventricular septal defects (VSD), interrupted aortic arch (IAA), aberrant left subclavian artery forming incomplete vascular ring and dual inferior vena cava (IVC), and right/left atrial isomerism. Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria/midline stomach, hypoplastic spleen/asplenia, left lung isomerism, and midline liver are also seen. Airway cilia are immotile.
In the second phenotype (associated with b2b2025.2Clo), cardiovascular defects involve double outlet right ventricle (DORV), hypoplastic pulmonary artery, atrioventricular septal defect (AVSD), right aortic arch (RAA), ventricular non-compaction, and aberrant left subclavian artery forming incomplete vascular ring. Right microphthalmia and syndactyly are also seen.
This ENU-induced mutation strain, carrying at least two mutations, was created and maintained on a C57BL/6J genetic background by the NHLBI Cardiovascular Development Consortium (CvDC), Bench to Bassinet Program. In the Ccdc39b2b2025.1Clo allele, a G-to-T single point mutation (c.G445T) was discovered through whole exome, high throughput sequencing. This mutation is predicted to result in the introduction of a stop codon at position 4390 (p.E149X) of the expressed protein. The second mutation, b2b2025.2Clo, has not been defined.
Allele Name | Bench to Bassinet Program (B2B/CVDC), mutation 2025 Cecilia Lo |
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Allele Type | Chemically induced (ENU) |
Allele Synonym(s) | Absolem |
Gene Symbol and Name | b2b2025Clo, Mutant line 2025 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | UN |
General Note | Summative Diagnosis: Mutant Type 1: Cardiovascular Phenotype: Heterotaxy presenting with dextrocardia/dextroversion and a spectrum of complex congenital heart disease such as superior-inferior ventricles, overriding aorta/double outlet right ventricle (DORV), DORV Taussig Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), perimembranous and muscular ventricular septal defects (VSD), interrupted aortic arch (IAA), aberrant left subclavian artery forming incomplete vascular ring and dual inferior vena cava (IVC), and right/left atrial isomerism Noncardiovascular Phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria/midline stomach, hypoplastic spleen/asplenia, left lung isomerism, and midline liver. Airway cilia are immotile Mutant Type 2: Cardiovascular phenotype: Double outlet right ventricle (DORV), hypoplastic pulmonary artery, atrioventricular septal defect (AVSD), right aortic arch (RAA), ventricular non-compaction, and aberrant left subclavian artery forming incomplete vascular ring Noncardiovascular phenotype: Right microphthalmia and syndactyly |