C57BL/6J-b2b2362Clo/J

Stock number: 022636
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Slit3 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 Slit3, slit homolog 3 (Drosophila) gene), animals demonstrate double outlet right ventricle (including Taussig-Bing subtype, DORV) with atrioventricular septal defect (AVSD), ventricular septal defects (VSD), and ventricular non-compaction. In one mutant this was accompanied by ectopia cordis. Gastroschisis with ectopia cordis is also seen. Homozygous b2b2362.2Clo animals show biventricular hypertrophy, and craniofacial defects including facial cleft/cleft lip, short snout, micrognathia, and dome shaped head.

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. The molecular lesion in the Slit3^b2b2362.1Clo mutation is attributed to a G-to-T single point mutation (c.G3538T, NM_011412) and is predicted to result in an amino acid substitution at codon 1180 (p.A1180S) of the expressed protein. The second mutation, b2b2362.2Clo, has not been defined.

Allele

Symbol: Slit3^b2b2362.1Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 2362, subline 1, Cecilia Lo
MGI accession ID: MGI:5560156
Generation method: Chemically induced (ENU)
Marker symbol: Slit3
Marker name: slit guidance ligand 3
Chromosome: 11
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 b2b2362Clo. The molecular lesion for this subline is attributed to a G to T substitution at coding nucleotide postion 3538 in exon 31 of the cDNA (c.3538G>T, NM_011412). This changes the alanine residue to serine at position 1180 of the expressed protein (p.A1180S).
General note: Summative Diagnosis:
Cardiovascular Phenotype: Double outlet right ventricle (including Taussig-Bing subtype, DORV) with atrioventricular septal defect (AVSD), ventricular septal defects (VSD), and ventricular non-compaction. In one mutant this was accompanied by ectopia cordis.
Noncardiovascular Phenotype (one mutant): Gastroschisis with ectopia cordis, hypoplastic kidneyl with some glomerular cysts

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
0170	Ectopia cordis
0606	DORV + AVSD (AV canal)
0610	DORV, Taussig bing
1300	Ventricular septal defect
1802	Excessive myocardial trabeculation or noncompaction
4414	Gastroschisis

Allele

Symbol: b2b2362.2Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2362, subline 2 Cecilia Lo
MGI accession ID: MGI:5560157
Generation method: Chemically induced (ENU)
Marker symbol: b2b2362.2Clo
Marker name: Mutant line 2362.2
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 b2b2362Clo.
General note: Summative Diagnosis:
Cardiovascular Phenotype: Biventricular hypertrophy
Noncardiovascular Phenotype: Craniofacial defect including facial cleft/cleft lip, short snout, micrognathia, and dome shaped head

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
3608	Left ventricular hypertrophy
3609	Right ventricular hypertrophy
4163	Micrognathia
4875	Cleft lip
7505	Biventricular hypertrophy

Allele

Symbol: b2b2362Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2362 Cecilia Lo
MGI accession ID: MGI:5560155
Generation method: Chemically induced (ENU)
Marker symbol: b2b2362Clo
Marker name: Mutant line 2362
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 Slit3^b2b2362.1Clo and b2b2362.2Clo
General note: Summative Diagnosis:
Mutant Type 1:
Cardiovascular Phenotype: Double outlet right ventricle (including Taussig-Bing subtype, DORV) with atrioventricular septal defect (AVSD), ventricular septal defects (VSD), and ventricular non-compaction. In one mutant this was accompanied by ectopia cordis.
Noncardiovascular Phenotype (one mutant): Gastroschisis with ectopia cordis, hypoplastic kidneyl with some glomerular cysts
Mutant Type 2:
Cardiovascular Phenotype: Biventricular hypertrophy
Noncardiovascular Phenotype: Craniofacial defect including facial cleft/cleft lip, short snout, micrognathia, and dome shaped head

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
0170	Ectopia cordis
0606	DORV + AVSD (AV canal)
0610	DORV, Taussig bing
1300	Ventricular septal defect
1802	Excessive myocardial trabeculation or noncompaction
4414	Gastroschisis
3608	Left ventricular hypertrophy
3609	Right ventricular hypertrophy
4163	Micrognathia
4875	Cleft lip
7505	Biventricular hypertrophy