C57BL/6J-b2b1879Clo/J

Stock number: 018240
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Adamts6 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 Adamts6 gene, homozygotes demonstrate cardiovascular defects that involve overriding aorta/double outlet right ventricle (DORV) with ventricular septal defects (subaortic, perimembranous, and muscular), atrioventricular septal defects (AVSD), and biventricular hypertrophy. Abnormal flexure of the hindlimbs, hydrops, midline fusion defect of the sternal vertebra, hypoplastic thymus, short snout, and cleft palate are also seen.

The b2b1879.2Clo mutation is associated with kidney agenesis.

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 Adamts6^b2b1879.1Clo allele, a C-to-G single point mutation (c.C447G, NM_001081020) was discovered through whole exome, high throughput sequencing. This mutation is predicted to result in a serine to arginine substitution at codon 149 (p.S149R) of the expressed protein. The second mutation, b2b1879.2Clo, has not been defined.

Allele

Symbol: b2b1879Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1879 Cecilia Lo
MGI accession ID: MGI:5476173
Generation method: Chemically induced (ENU)
Marker symbol: b2b1879Clo
Marker name: Mutant line 1879
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 b2b1879.1Clo and b2b1879.2Clo
General note: 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 b2b1879.1Clo and b2b1879.2Clo
Summative Diagnosis:
Mutant Type 1:
Cardiovascular Phenotype: Overriding aorta/Double outlet right ventricle (DORV) with ventricular septal defects (subaortic, perimembranous, and muscular), atrioventricular septal defects (AVSD), and biventricular hypertrophy
Noncardiovascular Phenotype: Abnormal flexure of the hindlimbs, hydrops, midline fusion defect of the sternal vertebra, hypoplastic thymus, short snout, and cleft palate

Mutant Type 2:
Noncardiac phenotype: Kidney agenesis

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)
1300	Ventricular septal defect
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1432	Overriding aortic valve
4100	Skeletal, skin, muscle anomaly
4876	Cleft palate
4906	Non-cardiac abnormality
7505	Biventricular hypertrophy
4503	Agenesis of kidneys

Allele

Symbol: Adamts6^b2b1879.1Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1879.1 Cecilia Lo
MGI accession ID: MGI:5476179
Generation method: Chemically induced (ENU)
Marker symbol: Adamts6
Marker name: a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 6
Chromosome: 13
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 b2b1879Clo. The molecular lesion for this subline is a C to G substitution at coding nucleotide 447 in exon 3 of the cDNA (c.447C>G, NM_001081020). This changes the serine residue to arginine at position 149 of the encoded protein (p.S149R).
General note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. It is a subline of b2b1879Clo.
Summative Diagnosis:
Cardiovascular Phenotype: Overriding aorta/Double outlet right ventricle (DORV) with ventricular septal defects (subaortic, perimembranous, and muscular), atrioventricular septal defects (AVSD), and biventricular hypertrophy
Noncardiovascular Phenotype: Abnormal flexure of the hindlimbs, hydrops, midline fusion defect of the sternal vertebra, hypoplastic thymus, short snout, and cleft palate

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)
1300	Ventricular septal defect
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1432	Overriding aortic valve
4100	Skeletal, skin, muscle anomaly
4876	Cleft palate
4906	Non-cardiac abnormality
7505	Biventricular hypertrophy

Allele

Symbol: b2b1879.2Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1879.2 Cecilia Lo
MGI accession ID: MGI:5476180
Generation method: Chemically induced (ENU)
Marker symbol: b2b1879.2Clo
Marker name: Mutant line 1879.2
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 b2b1879Clo.
General note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. It is a subline of b2b1879Clo.
Summative Diagnosis:
Noncardiac phenotype: Kidney agenesis

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
4503	Agenesis of kidneys