C57BL/6J-Tbc1d32^b2b2596Clo/J

Stock number: 022660
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Sensorineural Research

Description

This Tbc1d32 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-A point mutation in the Tbc1d32 (TBC1 domain family, member 32) gene 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 laterality defects, including PTA (Type A1), overriding aorta, atrioventricular septal defect (AVSD), dual inferior vena cava (IVC), and right atrial isomerism. Excencephaly, craniofacial defect with cleft lip/palate and failure in fusion of the frontonasal prominence, tracheoesophogeal fistula, hypoplastic lungs, eye defects such as anopthalmia and microphthalmia, polydactyly, and cystic/duplex kidneys 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. The molecular lesion is a C-to-A single point mutation at position 3096 of the cDNA (c.C3096A, NM_001033385) that is predicted to convert a tyrosine residue to a stop codon at position 1032 of the encoded protein (p.Y1032X).

Allele

Symbol: Tbc1d32^b2b2596Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2596 Cecilia Lo
MGI accession ID: MGI:5560497
Generation method: Chemically induced (ENU)
Marker symbol: Tbc1d32
Marker name: TBC1 domain family, member 32
Chromosome: 10
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 3096 in exon 27 of the cDNA (c.3096C>A, NM_001033385). This changes the tyrosine residue to a translation stop at position 1032 of the encoded protein (p.Y1032*).
General note: Summative Diagnosis:
Cardiovascular Phenotype (one mutant): PTA (Type A1), overriding aorta, atrioventricular septal defect (AVSD), dual inferior vena cava (IVC), and right atrial isomerism
Noncardiovascular Phenotype: Excencephaly, craniofacial defect with cleft lip/palate and failure in fusion of the frontonasal prominence, tracheoesophogeal fistula, hypoplastic lungs, eye defects such as anopthalmia and microphthalmia, polydactyly, cystic/duplex kidneys

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
0500	Truncus arteriosus
0510	Truncus arteriosus type i
1100	Atrioventricular canal (endocardial cushion defect)
1432	Overriding aortic valve
2810	Inferior vena cava anomaly
4103	Polydactyly
4134	Skull anomaly, congenital
4163	Micrognathia
4170	Hand and/or foot anomaly
4202	Tracheoesophageal fistula
4401	Cleft palate and cleft lip
4864	Anophthalmia
4875	Cleft lip
4876	Cleft palate
4877	Microphthalmia
4906	Non-cardiac abnormality