C57BL/6J-Megf8^b2b288Clo/J

Stock number: 013617
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This A3641T Megf8 (multiple EGF-like-domains 8) point mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease and development.

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 A3641T Megf8 (multiple EGF-like-domains 8) point 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 a double outlet right ventricle (DORV), transposition of great arteries, dextrocardia, and complete atroventricular septal defect (AVSD). Heterotaxia is also seen.

Development

This undefined 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. An A3641T (Ref seq NM_001160400) point mutation in Megf8 cDNA was discovered through whole exome, high throughput sequencing. This is predicted to alter an arginine residue to an isoleucine at position 1214 (N1214I) in the encoded protein.

Allele

Symbol: Megf8^b2b288Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 288 Cecilia Lo
MGI accession ID: MGI:5311364
Generation method: Chemically induced (ENU)
Marker symbol: Megf8
Marker name: multiple EGF-like-domains 8
Chromosome: 7
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh.The causitive molecular lesion for the cardiovascular phenotypes is an A to T substitution at coding nucleotide 3641 in exon 21 of the cDNA (c.3641A>T, NM_001160400). This changes the asparagine residue to isoleucine at position 1214 in the encoded protein (p.N1214I).
General note: Summative Diagnosis:
Cardiovascular defects: Hetertoaxy with complex congenital heart disease such as transposition of the great arteries (TGA;{SDD}) and dextrocardia with double outlet right ventricle (DORV;{ILL}).
Non-cardiac phenotype: Anopthalmia, short snout, micrognathia, 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
0190	Heterotaxy syndrome
0602	DORV, ventricular defect committed to aorta
0700	D-loop transposition of the great arteries
1120	Complete common atrioventricular canal
3804	Congenital heart disease
3950	{S,D,D}
3973	{I,L,L}
4846	Carpenter syndrome