C57BL/6J-Ift74^b2b796/J

Stock number: 018222
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Ift74 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 T-to-C point mutation at position 1645 of the Ift74 (intraflagellar transport 74) 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 syndrome (ambiguous lung lobation) with congenital heart disease (double outlet right ventricle (DORV), atrial-ventricular septal defect (AVSD) and dual inferior vena cava (IVC)).

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-C single point mutation at position 1645 of the cDNA (c.T1645C, NM_026319) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a tryptophan to arginine amino acid substitution at position 549 of the encoded protein (p.W549R).

Allele

Symbol: Ift74^b2b796Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 796 Cecilia Lo
MGI accession ID: MGI:5311374
Generation method: Chemically induced (ENU)
Synonyms: Princess Leia
Marker symbol: Ift74
Marker name: intraflagellar transport 74
Marker synonyms: 1700029H06Rik; b2b796Clo; BBS22; CCDC2; CMG1; CMG-1; JBTS40; SPGF58
Chromosome: 4
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 C substitution at coding nucleotide 1645 in exon 19 of the cDNA (c.1645T>C, NM_026319). This changes the tryptophan residue to arginine at position 549 of the encoded protein (p.W549R).
General note: Summative Diagnosis:
Cardiovascular phenotype: Heterotaxy syndrome (ambiguous lung lobation) with congenital heart disease: Double outlet right ventricle (DORV), atrial-ventricular septal defect (AVSD) and dual inferior vena cava (IVC)

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
0606	DORV + AVSD (AV canal)
1100	Atrioventricular canal (endocardial cushion defect)
1140	Common atrium
2810	Inferior vena cava anomaly
3804	Congenital heart disease
4235	Pulmonary malformation