C57BL/6J-b2b2025Clo/J

Stock number: 018257
Research areas: Cardiovascular Research, Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Sensorineural Research

Description

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.

Detailed description

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.

Development

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 Ccdc39^b2b2025.1Clo 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

Symbol: Ccdc39^b2b2025.1Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 2025, subline 1, Cecilia Lo
MGI accession ID: MGI:5554444
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. It is a subline of b2b2025Clo. The molecular lesion for this subline is attributed to a G-to-T substitution at coding nucleotide position 445 (c.445G>T) in exon 4 of the cDNA (c.445G>T). This changes the glutamic acid residue to a stop at position 149 of the expressed protein (p.E149*).
General note: Summative Diagnosis:
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

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
0600	Double outlet right ventricle
0606	DORV + AVSD (AV canal)
0610	DORV, Taussig bing
0110	Dextrocardia
0184	Superior-inferior ventricles (upstairs-downstairs ventricles)
0190	Heterotaxy syndrome
0800	L-loop transpostion of the great arteries
1100	Atrioventricular canal (endocardial cushion defect)
1250	Interrupted aortic arch
1300	Ventricular septal defect
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1432	Overriding aortic valve
2700	Abnormal aortic arch
2730	Aberrant left subclavian artery
2760	Vascular ring
2810	Inferior vena cava anomaly
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3950	{S,D,D}
3973	{I,L,L}
3983	{A,D,D}
4239	Left bronchial isomerism
4771	Asplenia

Allele

Symbol: b2b2025Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2025 Cecilia Lo
MGI accession ID: MGI:5491236
Generation method: Chemically induced (ENU)
Marker symbol: b2b2025Clo
Marker name: Mutant line 2025
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation line was isolated in a screen at the University of Pittsburgh. More than one mutation in this line results in a discernible phenotype in a homozygous recessive screen. At least two segregating phenotype groups are identified. See Ccdc39^b2b2025.1Clo and b2b2025.2Clo
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

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
0600	Double outlet right ventricle
0606	DORV + AVSD (AV canal)
0610	DORV, Taussig bing
0110	Dextrocardia
0184	Superior-inferior ventricles (upstairs-downstairs ventricles)
0190	Heterotaxy syndrome
0800	L-loop transpostion of the great arteries
1100	Atrioventricular canal (endocardial cushion defect)
1250	Interrupted aortic arch
1300	Ventricular septal defect
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1432	Overriding aortic valve
2700	Abnormal aortic arch
2730	Aberrant left subclavian artery
2760	Vascular ring
2810	Inferior vena cava anomaly
2966	Hypoplastic main pulmonary artery
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3950	{S,D,D}
3973	{I,L,L}
3983	{A,D,D}
4170	Hand and/or foot anomaly
4174	Syndactyly
4239	Left bronchial isomerism
4771	Asplenia
4877	Microphthalmia

Allele

Symbol: b2b2025.2Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2025, subline 2 Cecilia Lo
MGI accession ID: MGI:5554445
Generation method: Chemically induced (ENU)
Marker symbol: b2b2025.2Clo
Marker name: Mutant line 2025.2
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. It is a subline of b2b2025Clo.
General note: Summative Diagnosis:
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

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
0600	Double outlet right ventricle
0606	DORV + AVSD (AV canal)
1100	Atrioventricular canal (endocardial cushion defect)
1802	Excessive myocardial trabeculation or noncompaction
2700	Abnormal aortic arch
2720	Right aortic arch
2730	Aberrant left subclavian artery
2760	Vascular ring
2966	Hypoplastic main pulmonary artery
4170	Hand and/or foot anomaly
4174	Syndactyly
4877	Microphthalmia