C57BL/6J-Dync2h1^b2b414Clo/J

Stock number: 013620
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Sensorineural Research

Description

This single T701A point mutation in Dync2h1 (dynein cytoplasmic 2 heavy chain 1) cDNA 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 single T701A point mutation in Dync2h1 (dynein cytoplasmic 2 heavy chain 1) 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 here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.

Homozygotes demonstrate pulmonary atresia with ventricular septal defect (VSD), atrioventricular septal defect (AVSD), major aortopulmonary collateral arteries (MAPCA), coronary fistula, dual inferior vena cavae (IVC), and a single lung lobe. Micrognathia, hypotelorism, duplex kidney, polydactyly, syndactyly, oligodactyly, tracheoesphageal fistula (TEF), kidney agenesis, eye malformation, and mouth malformation 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 701 of the cDNA (c.T701A) was discovered through whole exome, high throughput sequencing after in an ENU screen for recessive cardiovascular development phenotypes. This change is predicted to result in a valine to glutamate change at position 234 of the encoded protein (p.V234E).

Allele

Symbol: Dync2h1^b2b414Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 414 Cecilia Lo
MGI accession ID: MGI:5311370
Generation method: Chemically induced (ENU)
Marker symbol: Dync2h1
Marker name: dynein cytoplasmic 2 heavy chain 1
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 T to A substitution at coding nucleotide 701 in exon 5 of the cDNA (c.701T>A, NM_029851). This changes the valine residue to glutamic acid at position 234 of the encoded protein (p.V234E).
General note: Summative Diagnosis:
Mutant Phenotype 1: Cardiovascular defects: Pulmonary atresia with ventricular septal defect (VSD), atrioventricular septal defect (AVSD), major aortopulmonary collateral arteries (MAPCA), coronary fistula, dual inferior vena cavae (IVC) and single lung lobe. Non-cardiovascular defects: Micrognathia, hypotelorism, duplex kidney, polydactyly/syndactyly/oligodactyly, and tracheoesphageal fistula (TEF).
Mutant Phenotype 2: Kidney agenesis, craniofacial anomalies.

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
0110	Dextrocardia
1081	Tetralogy of Fallot with pulmonary atresia and mapcas
1120	Complete common atrioventricular canal
1124	Balanced complete atrioventricular canal
1125	Unbalanced complete atrioventricular canal, left dominant
1140	Common atrium
2230	Coronary fistula (arterio-venous or arterio-cameral)
2810	Inferior vena cava anomaly
3100	Congenital coronary anomaly
3804	Congenital heart disease
3986	{A,D,S}
4044	VATERS/VACTERLS Syndrome
4103	Polydactyly
4163	Micrognathia
4170	Hand and/or foot anomaly
4174	Syndactyly
4202	Tracheoesophageal fistula
4232	Airway malformation
4235	Pulmonary malformation
4338	Holoprosencephaly
4503	Agenesis of kidneys
4863	Opthalmic malformation
4874	Mouth malformation