C57BL/6J-Cep290^b2b1454Clo/J

Stock number: 018204
Research areas: Cardiovascular Research, Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research

Description

This Cep290 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of heterotaxy, congenital heart disease, and polycystic kidney 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-A point mutation at position 4670 of the Cep290 (centrosomal protein 290) 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 disease associated with heterotaxy such as doublet outlet right ventricle, atrioventricular septal defect, duplicated inferior vena cava (IVC), and hypoplastic spleen/polysplenia. Cystic kidney with tubular and glomerular cysts, open eyes, and micrognathia 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-A single point mutation at position 4670 of the cDNA (c.T4670A, NM_146009) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a leucine to stop codon substitution at position 1557 of the encoded protein (p.L1557X).

Allele

Symbol: Cep290^b2b1454Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1454 Cecilia Lo
MGI accession ID: MGI:5437082
Generation method: Chemically induced (ENU)
Synonyms: Cep290^c.T4670A; Checkers
Marker symbol: Cep290
Marker name: centrosomal protein 290
Marker synonyms: 3H11Ag; b2b1454Clo; b2b1752Clo; BBS14; CT87; JBTS5; Kiaa; LCA10; MGC:7859; MKS4; Nphp6; POC3; rd16; RGD1311640; SLSN6
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 T to A substitution at coding nucleotide 4670 in exon 34 of the cDNA (c.4670T>A, NM_146009). This changes the leucine residue to a translation stop at position 1557 of the encoded protein (p.L1557*).
General note: Summative Diagnosis:
Cardiac phenotype: Congenital heart disease associated with heterotaxy such as doublet outlet right ventricle, atrioventricular septal defect, duplicated inferior vena cava (IVC), and hypoplastic spleen/polysplenia
Noncardiac phenotype: Cystic kidney tubular and glomerular cysts. Open eyes, micrognathia
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)
0600	Double outlet right ventricle
1100	Atrioventricular canal (endocardial cushion defect)
1340	Ventricular septal defect, ECD type
2810	Inferior vena cava anomaly
3804	Congenital heart disease
3983	{A,D,D}
4163	Micrognathia
4508	Polycystic kidney disease