C57BL/6J-Pcsk5^b2b1549Clo/J

Stock number: 018210
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research

Description

This Pcsk5 mutation was identified in a screen of ENU-induced mutations and may be useful in studies of congenital heart disease, primary ciliary dyskinesia, and heterotaxy.

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

A T-to-A mutation in Pcsk5 (proprotein convertase subtilisin/kexin type 5) 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 here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.

Homozygotes demonstrate heterotaxia with congenital heart diseases including dextrocardia/mesocardia, transposition of the great arteries (TGA), or double outlet right ventricle (DORV) and atrioventricular septal defect (AVSD). Immotile, hyperkinetic and dyskinetic airway cilia 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 4795 of the cDNA (c.T4795A, NM_001190483) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause a cysteine to serine amino acid substitution at position 1599 of the encoded protein (p.C1599S).

Allele

Symbol: Pcsk5^b2b1549Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1549 Cecilia Lo
MGI accession ID: MGI:5430343
Generation method: Chemically induced (ENU)
Marker symbol: Pcsk5
Marker name: proprotein convertase subtilisin/kexin type 5
Chromosome: 19
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 4795 in exon 35 of the cDNA (c.4795T>A, NM_001190483). This changes the cysteine residue to serine at position 1599 of the encoded protein (p.C1599S).Â
General note: Summative Diagnosis:
Heterotaxia with congenital heart diseases including dextrocardia/mesocardia, transposition of the great arteries (TGA), or double outlet right ventricle (DORV) and atrioventricular septal defect (AVSD)
Non-cardiac phenotype: Immotile, hyperkinetic and dyskinetic airway cilia

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
0110	Dextrocardia
140	Mesocardia
0190	Heterotaxy Syndrome
3804	Congenital heart disease
0606	DORV + AVSD (AV canal)
0700	D-loop transposition of the great arteries