C57BL/6J-Lrp2^b2b2671Clo/J

Stock number: 022653
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Sensorineural Research

Description

This Lrp2 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 Lrp2 (low density lipoprotein receptor-related protein 2) 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 persistent truncus arteriosis (PTA, Type A1, A2, A4), permembranous ventricular septal defects (pmVSD) and muscular ventricular septal defect (mVSD), right aortic arch (RAA), ventricular non-compaction, and ventricular hypertrophy. Short snout, anophthalmia/microphthalmia, short snount/micrognathia, hypoplastic thymus, incomplete closure of the umbilical herniation, cystic kidneys, hydrnephrosis, and hooked tail 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 C-to-A single point mutation at position 6612 of the cDNA (c.T6612A, NM_001033385) was discovered through whole exome, high throughput sequencing. This mutation is predicted to convert a tyrosine residue to a stop codon at position 2204 of the encoded protein (p.Y2204X).

Allele

Symbol: Lrp2^b2b2671Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 2671 Cecilia Lo
MGI accession ID: MGI:5560499
Generation method: Chemically induced (ENU)
Marker symbol: Lrp2
Marker name: low density lipoprotein receptor-related protein 2
Chromosome: 2
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 6612 in exon 39 of the cDNA (c.6612T>A, NM_001033385). This changes the tyrosine residue to a translation stop at position 2204 of the encoded protein (p.Y2204*).
General note: Summative Diagnosis:
Cardiovascular Phenotype: Persistent truncus arteriosis (PTA, Type A1, A2, A4), permembranous ventricular septal defects (pmVSD) and muscular ventricular septal defect (mVSD), right aortic arch (RAA), ventricular non-compaction, ventricular hypertrophy
Noncardiovascular Phenotype: Short snout, anophthalmia/microphthalmia, short snount/micrognathia, hypoplastic thymus, incomplete closure of the umbilical herniation, cystic kidneys, hydrnephrosis, hooked tail

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
1300	Ventricular septal defect
1310	Ventricular septal defect, membranous
1320	Ventricular septal defect, muscular
1802	Excessive myocardial trabeculation or noncompaction
2700	Abnormal aortic arch
2720	Right aortic arch
4163	Micrognathia
4502	Hydronephrosis
4864	Anophthalmia
4877	Microphthalmia
4906	Non-cardiac abnormality
4907	Non-cardiac thoracic abnormality
7505	Biventricular hypertrophy