C57BL/6J-Ccdc39^b2b1735Clo/J

Stock number: 018229
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Ccdc39 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.

Detailed description

A T-to-A point mutation in Ccdc39 (coiled-coil domain containing 39) 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 complex congenital heart disease (CHD) associated with heterotaxy such as double outlet right ventricle (DORV) with atrioventricular septal defect (AVSD), and dextrocardia associated with situs inversus totalis. Immotile airway cilia are also seen.

Development

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-A substitution at nucleotide +2 of an intron following nucleotide 357 of the cDNA (c.357+2T>A, NM_026222) was discovered through whole exome, high throughput sequencing. This mutation is presumed to be a splicing mutation.

Allele

Symbol: Ccdc39^b2b1735Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 1735, Cecilia Lo
MGI accession ID: MGI:5438066
Generation method: Chemically induced (ENU)
Marker symbol: Ccdc39
Marker name: coiled-coil domain containing 39
Chromosome: 3
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. The molecular lesion is a T to A substitution at nucleotide +2 following coding nucleotide 357 (c.357+2T>A, NM_026222) in intron 3, changing splice donor site A-GT to A-GA (wich is assumed to be much less efficient or inactive).
General note: Summative Diagnosis:
Cardiac phenotype: Cardiovascular phenotype: Dextrocardia and complex congenital heart defects associated with heterotaxy, including double outlet right ventricle (DORV) with atrioventricular septal defect (AVSD), and vascular ring. Also observed are mutants with situs inversus totalis without congenital heart defects
Non-Cardiac phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria and left lung isomerism. Also observed were micrognathia, short snout, and immotile airway cilia

Fyler Codes
The Fyler code developed by The Boston Children's Heart Foundation in Boston Children's Hospital provides a hierarchical clinical diagnosis of congenital cardiovascular defects and other disorders. These codes are used to delineate pathology in the mutant mouse models that parallel human disease and can be cross referenced to the International Pediatric and Congenital Cardiac Code (IPCCC) (http://www.ipccc.net/).

Fyler Code ID	Code Description
0100	Situs inversus totalis
0110	Dextrocardia
0190	Heterotaxy syndrome
0600	Double outlet right ventricle
2050	Atrial septal defect
2760	Vascular ring
3804	Congenital heart disease
3816	Abdominal situs inversus
3817	Abdominal situs ambiguous (abdominal heterotaxy)
4163	Micrognathia
4239	Left bronchial isomerism
4851	Kartagener syndrome (siewart syndrome)(primary ciliary dyskinesia)
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality