C57BL/6J-Adamts6^b2b2029Clo/J

Stock number: 018253
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease and other developmental defects.

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 mutation 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.

Homozygotes demonstrate cardiovascular defects that involve overriding aorta/double outlet right ventricle (DORV), thick aorta/pulmonary artery (Ao/PA) valves, dilated pulmonary artery (PA), hypoplastic aorta, biventricular hypertrophy, and coronary fistula. Craniofacial defects with micrognathia, hypoplastic thymus, unfused sternum, and hindlimb anomalies are also seen.

Development

This mutation, identified in an ENU screen for recessive cardiovascular development phenotypes, was created and maintained on a C57BL/6J genetic background by the NHLBI Cardiovascular Development Consortium (CvDC), Bench to Bassinet Program.

Allele

Symbol: Adamts6^b2b2029Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2029 Cecilia Lo
MGI accession ID: MGI:5487287
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. The molecular lesion 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: 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