C57BL/6J-Ap2b1^b2b2321Clo/J

Stock number: 022640
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Ap2b1 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 T-to-A point mutation at position 5503 of the Ap2b1 (adaptor-related protein complex 2, beta 1 subunit) 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 overriding aorta/double outlet right ventricle (DORV, Taussig-Bing subtype) with atrioventricular septal defect (AVSD), perimembranous ventricular septal defect (VSD), right aortic arch (RAA), and ventricular hypertrophy. Micrognathia, cleft palate, and hypoplastic thymus are also seen.

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. A T-to-A single point mutation at position 1343 of the cDNA (c.T1343A, NM_027915) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a methionine to lysine amino acid substitution at position 448 of the encoded protein (p.M448K).

Allele

Symbol: Ap2b1^b2b2321Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2321 Cecilia Lo
MGI accession ID: MGI:5552944
Generation method: Chemically induced (ENU)
Marker symbol: Ap2b1
Marker name: adaptor-related protein complex 2, beta 1 subunit
Chromosome: 11
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 T to A substitution at position 1343 of the cDNA (c.1343T>A, NM_027915). This changes the methionine residue to lysine at position 448 of the encoded protein (p.M448K).
General note: Summative Diagnosis:
Cardiovascular phenotype: Overriding aorta/double outlet right ventricle (DORV, Taussig-Bing subtype) with atrioventricular septal defect (AVSD), perimembranous ventricular septal defect (VSD), right aortic arch (RAA), and ventricular hypertrophy
Noncardiovascular phenotype: Micrognathia, cleft palate, and hypoplastic 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
0606	DORV + AVSD (AV canal)
0610	DORV, Taussig bing
1100	Atrioventricular canal (endocardial cushion defect)
1310	Ventricular septal defect, membranous
1432	Overriding aortic valve
2700	Abnormal aortic arch
2720	Right aortic arch
3608	Left ventricular hypertrophy
3609	Right ventricular hypertrophy
4163	Micrognathia
4876	Cleft palate
4906	Non-cardiac abnormality
7505	Biventricular hypertrophy