C57BL/6J-b2b2736Clo/J

Stock number: 022677
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Sensorineural Research

Description

This Cfc1 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 Cfc1 (cripto, FRL-1, cryptic family 1) gene, homozygotes demonstrate Cardiovascular Phenotype: Complex congenital heart defects associated with heterotaxy, such as dextroversion with transposition of the great arteries (TGA), unbalanced atrioventricular ventricular septal defect (AVSD), muscular ventricular septal defects (mVSD), hypoplastic right ventricle (RV), common atrium, right aortic arch (RAA), right atrial isomerism, aberrant right subclavian artery, bilateral patent ductus arteriosus (PDA) forming vascular ring, superior-inferior ventricles, and total anomalous pulmonary venous return (TAPVR, intracardiac type). Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right bronchial isomerism, polysplenia, left liver isomerism, inverted liver lobation, malaligned sternal vertebra, and hypoplastic spleen are also seen.

The b2b2736.2Clo mutation is associated with Persistent truncus arteriosus (PTA, Type 1), atrioventricular ventricular septal defect (AVSD), right aortic arch (RAA), and aberrant left subclavian artery forming vascular ring. Growth retardation, microphthalmia, syndactyly, micrognathia, cleft palate, hypoplastic kidneys, lungs, and thymus.

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 Cfc1^b2b2736.1Clo allele, the molecular lesion is a G-to-A substitution at nucleotide +1 of an intron after nucleotide 103 (c.103+1G>A, NM_007685), a presumed splicing mutation. The second mutation, b2b2736.2Clo, has not been defined.

Allele

Symbol: Cfc1^b2b2736.1Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 2736.1, Cecilia Lo
MGI accession ID: MGI:5560815
Generation method: Chemically induced (ENU)
Marker symbol: Cfc1
Marker name: cripto, FRL-1, cryptic family 1
Chromosome: 1
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 b2b2736Clo. The molecular lesion is a G to A substitution at nucleotide +1 after coding nucleotide 103 (c.103+1G>A, NM_007685) in intron 2, changing splice donor site A-GT to A-AT (which is assumed to be inactive or much less efficient).
General note: Summative Diagnosis:
Mutant Type 1: Cardiovascular Phenotype: Complex congenital heart defects associated with heterotaxy, such as dextroversion with transposition of the great arteries (TGA), unbalanced atrioventricular ventricular septal defect (AVSD), muscular ventricular septal defects (mVSD), hypoplastic right ventricle (RV), common atrium, right aortic arch (RAA), right atrial isomerism, aberrant right subclavian artery, bilateral patent ductus arteriosus (PDA) forming vascular ring, superior-inferior ventricles, and total anomalous pulmonary venous return (TAPVR, intracardiac type)
Noncardiovascular Phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right bronchial isomerism, polysplenia, left liver isomerism, inverted liver lobation, malaligned sternal vertebra, and hypoplastic spleen

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
1100	Atrioventricular canal (endocardial cushion defect)
2700	Abnormal aortic arch
2760	Vascular ring
4906	Non-cardiac abnormality
0184	Superior-inferior ventricles (upstairs-downstairs ventricles)
0190	Heterotaxy Syndrome
0700	D-loop transposition of the great arteries
1140	Common atrium
1300	Ventricular septal defect
1320	Ventricular septal defect, muscular
1821	Hypoplastic right ventricle (subnormal cavity volume)
2731	Aberrant right subclavian artery
4100	Skeletal, skin, muscle anomaly
4240	Right bronchial isomerism
4907	Non-cardiac thoracic abnormality

Allele

Symbol: b2b2736Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2736 Cecilia Lo
MGI accession ID: MGI:5560813
Generation method: Chemically induced (ENU)
Marker symbol: b2b2736Clo
Marker name: Mutant line 2736
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 Cfc1^b2b2736.1Clo and b2b2736.2Clo
General note: Summative Diagnosis:
Mutant Type 1: Cardiovascular Phenotype: Complex congenital heart defects associated with heterotaxy, such as dextroversion with transposition of the great arteries (TGA), unbalanced atrioventricular ventricular septal defect (AVSD), muscular ventricular septal defects (mVSD), hypoplastic right ventricle (RV), common atrium, right aortic arch (RAA), right atrial isomerism, aberrant right subclavian artery, bilateral patent ductus arteriosus (PDA) forming vascular ring, superior-inferior ventricles, and total anomalous pulmonary venous return (TAPVR, intracardiac type)
Noncardiovascular Phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right bronchial isomerism, polysplenia, left liver isomerism, inverted liver lobation, malaligned sternal vertebra, and hypoplastic spleen

Mutant Type 2:
Cardiovascular Phenotype: Persistent truncus arteriosus (PTA, Type 1), atrioventricular ventricular septal defect (AVSD), right aortic arch (RAA), and aberrant left subclavian artery forming vascular ring
Noncardiovascular Phenotype: growth retardation, microphthalmia, syndactyly, micrognathia, cleft palate, hypoplastic kidneys, lungs, and thymus

Phenotypic Similarity to Human Syndrome:
Mutant Type 1: Heterotaxy

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
1100	Atrioventricular canal (endocardial cushion defect)
2700	Abnormal aortic arch
2760	Vascular ring
4906	Non-cardiac abnormality
0184	Superior-inferior ventricles (upstairs-downstairs ventricles)
0190	Heterotaxy Syndrome
0700	D-loop transposition of the great arteries
1140	Common atrium
1300	Ventricular septal defect
1320	Ventricular septal defect, muscular
1821	Hypoplastic right ventricle (subnormal cavity volume)
2731	Aberrant right subclavian artery
4100	Skeletal, skin, muscle anomaly
4240	Right bronchial isomerism
4907	Non-cardiac thoracic abnormality
0510	Truncus arteriosus type i
2720	Right aortic arch
2730	Aberrant left subclavian artery
4170	Hand and/or foot anomaly
4174	Syndactyly

Allele

Symbol: b2b2736.2Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2736.2 Cecilia Lo
MGI accession ID: MGI:5560812
Generation method: Chemically induced (ENU)
Marker symbol: b2b2736.2Clo
Marker name: Mutant line 2736.2
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 b2b2736Clo.
General note: Summative Diagnosis:

Mutant Type 2:
Cardiovascular Phenotype: Persistent truncus arteriosus (PTA, Type 1), atrioventricular ventricular septal defect (AVSD), right aortic arch (RAA), and aberrant left subclavian artery forming vascular ring
Noncardiovascular Phenotype: growth retardation, microphthalmia, syndactyly, micrognathia, cleft palate, hypoplastic kidneys, lungs, and thymus

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
1100	Atrioventricular canal (endocardial cushion defect)
2700	Abnormal aortic arch
2760	Vascular ring
4906	Non-cardiac abnormality
0510	Truncus arteriosus type i
2720	Right aortic arch
2730	Aberrant left subclavian artery
4170	Hand and/or foot anomaly
4174	Syndactyly