C57BL/6J-Mmp21^b2b2458Clo/J

Stock number: 022650
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Mmp21 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 in the Mmp21 (matrix metallopeptidase 21) 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 complex congenital heart disease associated with heterotaxy, such as dextrocardia, double outlet right ventricle (DORV) or DORV Taussig-Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), superior-inferior ventricles, and hypoplastic right ventricle (RV). Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right pulmonary isomerism, malaligned sternal vertebrae, and inverted liver lobation are also seen. Micrognathia is also observed.

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 973 of the cDNA (c.T973A, NM_152944) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an amino acid substitution at position 325 of the encoded protein (p.Y325N).

Allele

Symbol: Mmp21^b2b2458Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2458 Cecilia Lo
MGI accession ID: MGI:5554438
Generation method: Chemically induced (ENU)
Marker symbol: Mmp21
Marker name: matrix metallopeptidase 21
Chromosome: 7
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 coding nucleotide 973 in exon 4 of the cDNA (c.973T>A, NM_152944). This changes the tyrosine residue to asparagine at position 325 of the encoded protein (p.Y325N).
General note: Summative Diagnosis:
Cardiovascular phenotype: Complex congenital heart disease associated with heterotaxy, such as dextrocardia, double outlet right ventricle (DORV) or DORV Taussig-Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), superior-inferior ventricles, and hypoplastic right ventricle (RV)
Noncardiovascular phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right pulmonary isomerism, malaligned sternal vertebrae, and inverted liver lobation. Also observed were micrognathia.

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)
0610	DORV, Taussig bing
0190	Heterotaxy syndrome
0700	D-loop transposition of the great arteries
1100	Atrioventricular canal (endocardial cushion defect)
1821	Hypoplastic right ventricle (subnormal cavity volume)
4100	Skeletal, skin, muscle anomaly
4163	Micrognathia
4240	Right bronchial isomerism
4400	Gastrointestinal anomaly
4906	Non-cardiac abnormality