C57BL/6J-b2b1625Clo/J

Stock number: 018197
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Sensorineural Research

Description

These Snx17 and Lrp2 mutations were 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 mutant strain, carrying at least two mutations, 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.

Two mutant phenotypes are observed. In the first (associated with the Snx17 gene, sorting nexin 17), homozygotes demonstrate double outlet right ventricle (DORV)/overriding aorta (Ao), and atrioventricular septal defect (AVSD). Anopthalmia and duplex kidneys are also seen.

In the second phenotype (associated with the Lrp2 gene, low density lipoprotein receptor-related protein 2), persistent truncus arteriosus (PTA), aortic arch anomalies, and vascular ring are seen. Agnathia, microstomia, holoprosencephaly, omphalocele, and low set ears are also seen.

Development

This ENU-induced mutation strain, carrying at least two mutations, was created and maintained on a C57BL/6J genetic background by the NHLBI Cardiovascular Development Consortium (CvDC), Bench to Bassinet Program. In the Snx17^b2b1625.1Clo allele, an A-to-G single point mutation at position 431 of the cDNA (c.A431G, NM_153680) was discovered through whole exome, high throughput sequencing. This mutation is predicted to cause an amino acid substitution at position 4144 of the encoded protein (p.E144G). In the Lrp2^b2b1625.2Clo allele, an A-to-G single point mutation at position -3 of the cDNA (c.8456-3A>G, NM_001081088) was discovered through whole exome, high throughput sequencing. This mutation is a presumed splicing mutation.

Allele

Symbol: b2b1625Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1625 Cecilia Lo
MGI accession ID: MGI:5438060
Generation method: Chemically induced (ENU)
Synonyms: Tupac
Marker symbol: b2b1625Clo
Marker name: Mutant line 1625
Chromosome: UN
Strain of origin: C57BL/6J
Molecular note: This ENU-induced mutation line was isolated in a screen at the University of Pittsburgh. More than one mutation in this line results in a discernible phenotype in a homozygous recessive screen. At least two segregating phenotype groups are identified. See b2b1625.1Clo and b2b1625.2Clo
General note: This ENU-induced mutation line was isolated in a screen at the University of Pittsburgh. More than one mutation in this line results in a discernible phenotype in a homozygous recessive screen. At least two segregating phenotype groups are identified. See b2b1625.1Clo and b2b1625.2Clo

Summative Diagnosis:
Mutant Type 1:
Cardiac phenotype: Double outlet right ventricle (DORV)/overriding aorta (Ao), atrioventricular septal defect (AVSD)
Noncardiac phenotype: Anopthalmia, duplex kidneys

Mutant Type 2:
Cardiac phenotype: Persistent truncus arteriosus (PTA), aortic arch anomalies, vascular ring
Noncardiac phenotype: Agnathia, microstomia, holoprosencephaly, omphalocele, low set ears

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
0510	Truncus arteriosus type i
0600	Double outlet right ventricle
1100	Atrioventricular canal (endocardial cushion defect)
1432	Overriding aortic valve
4404	omphalocele
4864	Anophthalmia
2760	Vascular ring

Allele

Symbol: Snx17^b2b1625.1Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1625, subline 1 Cecilia Lo
MGI accession ID: MGI:5489924
Generation method: Chemically induced (ENU)
Marker symbol: Snx17
Marker name: sorting nexin 17
Marker synonyms: 5830447M19Rik; b2b1625.1Clo; D5Ertd260e; mKIAA0064
Chromosome: 5
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 b2b1625Clo. The molecular lesion is an A to G substituation at coding nucleotide 431 in exon 5 of the cDNA (c.431A>G, NM_153680). This changes the glutamic acid residue to glycine at position 144 of the encoded protein (p.E144G).
General note: This mutation is present in a subline of b2b1625Clo.

Summative Diagnosis:
Cardiac phenotype: Double outlet right ventricle (DORV)/overriding aorta (Ao), atrioventricular septal defect (AVSD)
Noncardiac phenotype: Anopthalmia, 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
0600	Double outlet right ventricle
1100	Atrioventricular canal (endocardial cushion defect)
1432	Overriding aortic valve
4864	Anophthalmia

Allele

Symbol: Lrp2^b2b1625.2Clo
Name: Bench to Bassinet Program (B2B/CVDC), mutation 1625, subline 2 Cecilia Lo
MGI accession ID: MGI:5489925
Generation method: Chemically induced (ENU)
Marker symbol: Lrp2
Marker name: low density lipoprotein receptor-related protein 2
Marker synonyms: b2b1625.2Clo; D230004K18Rik; DBS; Gp330; LRP-2; Megalin
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 b2b1625Clo. The molecular lesion is an A to G substitution at nucleotide -3 before coding nucleotide 8456 (c.8456-3A>G, NM_001081088) in intron 44. This changes splice acceptor site AAG to TAG (which may have a different efficiency).
General note: This mutation is present in a subline of b2b1625Clo.

Summative Diagnosis:
Cardiac phenotype: Persistent truncus arteriosus (PTA), aortic arch anomalies, vascular ring
Noncardiac phenotype: Agnathia, microstomia, holoprosencephaly, omphalocele, low set ears

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
0510	Truncus arteriosus type i
4404	omphalocele
2760	Vascular ring