C57BL/6J-Dnah11^b2b1289Clo/J

Stock number: 018196
Research areas: Cardiovascular Research, Developmental Biology Research, Endocrine Deficiency 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 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-G point mutation at position 5632 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 congenital heart defects associated with heterotaxy such as vascular sling with isolated left subclavian artery, right aortic arch, muscular vascular septal defect (VSD) and biventricular hypertrophy. A midline liver, left pulmonary isomerism, polysplenia and duplex kidney 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 T-to-G single point mutation at position 5632 of the cDNA (c.A5632G, NM_010060) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an threonine to alanine amino acid substitution at position 1878 of the encoded protein (p.T1878A).

Allele

Symbol: Dnah11^b2b1289Clo
Name: Bench to Bassinet Program (B2B/CVDC) mutation 1289, Cecilia Lo
MGI accession ID: MGI:5437083
Generation method: Chemically induced (ENU)
Marker symbol: Dnah11
Marker name: dynein, axonemal, heavy chain 11
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 G substitution at coding nucleotide position 5632 in exon 33 of the cDNA (c.5632A>G, NM_010060). This changes the threonine residue to alanine at position 1878 of the encoded protein (p.T1878A).
General note: Summative Diagnosis:
Cardiovascular phenotype: Congenital heart defects associated with heterotaxy such as vascular sling with isolated left subclavian artery, right aortic arch (RAA), muscular vascular septal defect (VSD), and biventricular hypertrophy
Noncardiovascular phenotype: Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, midline liver, left pulmonary isomerism, polysplenia, hypoplastic spleen, and malaligned sternal vertebra. Also observed was anophthalmia/microphthalmia, and duplex, cystic, and hydronephrotic kidney with hydroureter

Phenotypic Similarity to Human Syndrome: Heterotaxy, Polysplenia syndrome (left isomerism), Primary Ciliary Dyskinesia (PCD)

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
0190	Heterotaxy Syndrome
0192	Polysplenia syndrome (left isomerism)
1300	Ventricular septal defect
1320	Ventricular septal defect, muscular
2700	Abnormal aortic arch
2720	Right aortic arch
2732	Isolation of the left subclavian artery
2760	Vascular ring
3804	Congenital heart disease
3817	Abdominal situs ambiguous (abdominal heterotaxy)
4100	Skeletal, skin, muscle anomaly
4239	Left bronchial isomerism
4502	Hydronephrosis
4508	Polycystic kidney disease
4512	Renal malformation
4864	Anophthalmia
4877	Microphthalmia
7505	Biventricular hypertrophy