C57BL/6J-Cntrl^b2b1468.1Clo/J

Stock number: 013693
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Cep110 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 1886 of the Cep110 (centrosomal protein 110) 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 double outlet right ventricle (DORV), atrioventricular septal defect (AVSD), ventricular septal defects (VSD), and hypoplastic right heart syndrome. Cystic kidney and hydronephrosis are also seen. This strain may be useful as a model of nephronophthisis, Meckel Gruber Syndrome, or Hypoplastic Right Heart Syndrome (HRHS).

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 1886 of the cDNA (c.T1886C, NM_012018) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause isoleucine to threonine amino acid substitution at position 1629 of the encoded protein (p.I1629T).

Allele

Symbol: Cntrl^b2b1468.1Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1468, subline 1 Cecilia Lo
MGI accession ID: MGI:5438058
Generation method: Chemically induced (ENU)
Marker symbol: Cntrl
Marker name: centriolin
Chromosome: 2
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation was isolated in a screen at the University of Pittsburgh. It is a subline of b2b1468Clo. The molecular lesion for this subline is a T to C substitution at coding nucleotide 1886 in exon 13 (c.1886T>C, NM_012018). This changes the isoleucine residue to threonine at position 629 in the encoded protein (p.I629T).
General note: Summative Diagnosis:
Cardiovascular phenotypes: Double outlet right ventricle (DORV), atrioventricular septal defect (AVSD), ventricular septal defects (VSD)

Noncardiovascular phenotype: Cystic kidney, tubular dilations, hydroureter, and hydronephrosis

Phenotypic Similarity to Human Syndrome:
Nephronophthisis



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 Codes	Code Description
600	Double outlet right ventricle
1300	Ventricular septal defect
1821	Hypoplastic right ventricle (subnormal cavity volume)
2050	Atrial septal defect
4502	Hydronephrosis
4508	Polycystic kidney disease