C57BL/6J-Dnah11^b2b1203Clo/J

Stock number: 018223
Research areas: Cardiovascular 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 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-T point mutation at position 2755 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 heterotaxy with congenital heart disease. Duplex kidneys with kidney cysts are also seen. Tracheal airway cilia are mostly immotile with some displaying hyperkinetic beat.

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-T single point mutation at position 2755 of the cDNA (c.C10243T, NM_010060) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a glutamine to a stop codon substitution at position 919 of the encoded protein (p.Q3415X).

Allele

Symbol: Dnah11^b2b1203Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 1203, Cecilia Lo
MGI accession ID: MGI:5311388
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 a C to T substitution at coding nucleotide position 2755 in exon 63 of the cDNA (c.10243C>T, NM_010060). This changes the glutamine residue to a stop codon at position 3415 of the encoded protein (p.Q3415*).
General note: Summative Diagnosis:
Cardiovascular phenotype: Situs inversus totalis and heterotaxy with congenital heart disease, such as dextrocardia, dual inferior vena cava (IVC), and right aortic arch (RAA)
Noncardiovascular phenotype: Situs inversus totalis as well as abnormal thoracic and abdominal organ situs anomalies associated with heterotaxy, such as dextrogastria, inverted lung lobation, and inverted liver lobation. Also observed were duplex kidneys with kidney cysts. Tracheal airway cilia are mostly immotile with some displaying hyperkinetic beat

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
2700	Abnormal aortic arch
2720	Right aortic arch
2810	Inferior vena cava anomaly
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
4512	Renal malformation
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality