C57BL/6J-Dnah5^b2b601Clo/J

Stock number: 013663
Research areas: Cardiovascular Research, Developmental Biology 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 phenotype is similar to that of human Primary Ciliary Dyskinesia, Kartagener's syndrome, and Heterotaxy.

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 (c.438+2T-A) in Dnah5 (dynein, axonemal, heavy chain 5) 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 heterotaxy with abdominal situs ambiguous and congenital heart disease (CDH) that includes dextrocardia wih double outlet right ventricle (DORV) and atrioventricular septal defect (AVSD). Immotile airway cilia with an outer dynein arm defect are also seen. The phenotype is similar to that of human Primary Ciliary Dyskinesia, Kartagener's syndrome, and Heterotaxy.

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- point mutation (c.438+2T-A) in Dnah5 was discovered through whole exome, high throughput sequencing (c.438+2T-A).

Allele

Symbol: Dnah5^b2b601Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 601 Cecilia Lo
MGI accession ID: MGI:5311153
Generation method: Chemically induced (ENU)
Marker symbol: Dnah5
Marker name: dynein, axonemal, heavy chain 5
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 T to A substitution at nucleotide +2 after coding nucleotide 438 (c.438+2T>A, NM_133365) in intron 4. This changes splice donor site G-GT to G-GA (which is assumed to be inactive).
General note: Summative Diagnosis:
Cardiovascular defect: Situs inversus totalis and heterotaxy with abdominal situs ambigous and congenital heart disease: Dextrocardia with double outlet right ventricle (DORV) and atrioventricular septal defect (AVSD).
Non-cardiovascular defect: Immotile airway cilia with outer dynein arm defect.

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
0140	Mesocardia
0606	DORV + AVSD (AV canal)
1100	Atrioventricular canal (endocardial cushion defect)
2720	Right aortic arch
3817	Abdominal situs ambiguous (abdominal heterotaxy)
3974	{I,L,I}