C57BL/6J-Smad6^b2b390Clo/J

Stock number: 013622
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Smad6 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

This A-to-T point mutation at position 982 of the Smad6 (SMAD family member 6) 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 cardiovascular defects that involve a transposition of the great arteries (D-TGA), double outlet right ventricle (DORV), and ventricular septal defects (VSD).

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. An A-to-T single point mutation at position 982 of the cDNA (c.A982T, NM_008542) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a lysine to a stop codon substitution at position 328 of the encoded protein (p.K328X).

Allele

Symbol: Smad6^b2b390Clo
Name: Bench to Bassinet Program (B2B/CvDC), mutation 390 Cecilia Lo
MGI accession ID: MGI:5316777
Generation method: Chemically induced (ENU)
Marker symbol: Smad6
Marker name: SMAD family member 6
Marker synonyms: AOVD2; b2b390Clo; HsT17432; MADH6; MADH7; Smad 6
Chromosome: 9
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 A to T substitution at coding nucleotide 982 in exon 4 of the cDNA (c.982A>T, NM_008542). This changes the lysine residue to a stop at position 328 of the encoded protein (p.K328*).
General note: Summative Diagnosis:
Cardiovascular defects: Transposition of the great arteries (D-TGA), double outlet right ventricle (DORV), and ventricular septal defects (VSD).

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
0400	Tricuspid atresia
0600	Double outlet right ventricle
0700	D-loop transposition of the great arteries
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1432	Overriding aortic valve
3804	Congenital heart disease