C57BL/6J-Dnah5^b2b1154Clo/J

Stock number: 013687
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Dnah5 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 C-to-A single point mutation at position 2755 of the Dnah5 (dynein, axonemal, heavy chain 5) 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 heterotaxy with congenital heart disease and situs inversus totalis. Immotile 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 C-to-A single point mutation at position 2755 of the cDNA (c.C2755A, NM_133365) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a histidine to asparagine amino acid substitution at position 919 of the encoded protein (p.H919N).

Allele

Symbol: Dnah5^b2b1154Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1154 Cecilia Lo
MGI accession ID: MGI:5311386
Generation method: Chemically induced (ENU)
Marker symbol: Dnah5
Marker name: dynein, axonemal, heavy chain 5
Marker synonyms: b2b1134Clo; b2b1154Clo; b2b1537Clo; b2b1565Clo; b2b3491Clo; CILD3; DLP5; Dnahc5; Dnahc8; HL1; KTGNR; Mdnah5; PCD
Chromosome: 15
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 C to A substitution at coding nucleotide 2755 in exon 19 of the cDNA (c.2755C>A, NM_133365). This changes the histidine residue to asparagine at position 919 of the encoded protein (p.H919N).
General note: Summative Diagnosis:
Cardiovascular phenotype: Situs inversus totalis and heterotaxy with congenital heart disease including dextrocardia, double outlet right ventricle (DORV), atrioventricular septal defects (AVSD), and right atrial isomerism (RAI)
Noncardiovascular phenotype: Situs inversus totalis and abnormal thoracic and abdominal organ situs anomalies associated with heterotaxy, such as dextrogastria, left liver isomerism, left lung isomerism, and malaligned sternal vertebra. Airway cilia were immotile

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
0606	DORV + AVSD (AV canal)
1100	Atrioventricular canal (endocardial cushion defect)
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3974	{I,L,I}
4100	Skeletal, skin, muscle anomaly
4239	Left bronchial isomerism
4851	Kartagener syndrome (siewart syndrome)(primary ciliary dyskinesia)