C57BL/6J-Dnah11^b2b598Clo/J

Stock number: 013659
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research

Description

This Dnah11 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of heterotaxy, congenital heart disease, and kidney defects.

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 C3184T Dnah11 (dynein, axonemal, heavy chain 11) 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 described here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.

Homozygotes demonstrate laterality defects, including situs inversus totalis, heterotaxy, left pulmonary isomerism and left liver isomerism. Cystic kidney disease, hydronephrosis, and hyperkinetic/dyskinetic airway cilia 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 C3184T point mutation in the Dnah11 cDNA (Ref seq NM_010060) was discovered through whole exome, high throughput sequencing. This is predicted to alter an arginine residue to an isoleucine at position 1214 (p.Q1062X) in the encoded protein.

Allele

Symbol: Dnah11^b2b598Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 598, Cecilia Lo
MGI accession ID: MGI:5311372
Generation method: Chemically induced (ENU)
Synonyms: Joplin
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 causitive molecular lesion for the cardiovascular phenotypes is a C to T substitution at coding nucleotide postition 3184 in exon 16 of the cDNA (c.3184C>T, NM_010060). This changes the glutamine residue to a stop codon at position 1062 in the encoded protein (p.Q1062*).
General note: Summative Diagnosis:
Cardiovascular phenotype: Situs inversus totalis, dextrocardia with muscular ventricular septal defect (VSD), ventricular myocardial non-compaction.
Noncardiovascular phenotype: Situs inversus totalis as well as heterotaxy with abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, left pulmonary isomerism, and malaligned sternal vertebra. Also observed were cystic kidneys and hydronephrosis. Airway cilia were hyperkinetic/dyskinetic

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
1300	Ventricular septal defect
1320	Ventricular septal defect, muscular
1802	Excessive myocardial trabeculation or noncompaction
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3974	{I,L,I}
4100	Skeletal, skin, muscle anomaly
4239	Left bronchial isomerism
4502	Hydronephrosis
4508	Polycystic kidney disease