C57BL/6J-Dnah11^b2b1279Clo/J

Stock number: 013696
Research areas: Cardiovascular Research, Developmental Biology Research

Description

This Dnah11 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of heterotaxy and 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 A-to-T point mutation at position 10369 of the Dnah11 (dynein, axonemal, heavy chain 11) 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 situs inversus totalis and heterodoxy with congenital heart disease including transposition of the great arteries (d-TGA) with ventricular septal defects (VSD). Airway cilia show a wide range of motion defects including immotility, hyperkinetic beat, dyskinetic and slow cilia motility.

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. An A-to-T single point mutation at position 10369 of the Dnah11 cDNA (c.A10369T, NM_010060) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an isoleucine to a phenylalanine substitution at position 3457 of the encoded protein (p.I3457F).

Allele

Symbol: Dnah11^b2b1279Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 1279, Cecilia Lo
MGI accession ID: MGI:5311393
Generation method: Chemically induced (ENU)
Marker symbol: Dnah11
Marker name: dynein, axonemal, heavy chain 11
Marker synonyms: avc4; b2b1203Clo; b2b1279Clo; b2b1289Clo; b2b1727Clo; b2b598Clo; CILD7; DNAHBL; Dnahc11; DNHBL; DPL11; lrd
Chromosome: 12
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 an A to T substitution at coding nucleotide position 10369 in exon 64 of the cDNA (c.10369A>T, NM_010060). This changes the isoleucine residue to phenylalanine at position 3457 of the encoded protein (p.I3457F).
General note: Summative Diagnosis:
Cardiovascular phenotype: Situs inversus totalis and heterotaxy presenting with spectrum of congenital heart disease, including dextrocardia, transposition of the great arteries (d-TGA), double outlet right ventricle (DORV) with atrioventricular (AVSD) ventricular septal defects (VSD), mitral valve atresia, and ventricular non-compaction
Noncardiovascular phenotype: Situs inversus totalis and abnormal thoracic and abdominal organ situs anomalies associated with heterotaxy, such as dextrogastria, hypoplastic spleen, left lung isomerism, and malaligned sternal vertebra. Also observed was micrognathia and airway cilia showing a wide range of motion defects including immotility, hyperkinetic beat, dyskinetic and slow cilia motility.

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
0100	Situs inversus totalis
0110	Dextrocardia
0190	Heterotaxy syndrome
0600	Double outlet right ventricle
0700	D-loop transposition of the great arteries
1100	Atrioventricular canal (endocardial cushion defect)
1300	Ventricular septal defect
1508	Mitral valve abnormality
1802	Excessive myocardial trabeculation or noncompaction
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
4100	Skeletal, skin, muscle anomaly
4163	Micrognathia
4239	Left bronchial isomerism
4906	Non-cardiac abnormality