C57BL/6J-Notch3^hpbk/GrsrJ

Stock number: 005330
Product name: humpback

Description

These mice carry an ENU-induced mutation at the Notch3 locus and exhibit myopathy.

Detailed description

Mice homozygous for the humpback mutation appear normal at wean age, but by 5 weeks of age can be distinguished by thoracic kyphosis and scrawniness. Both phenotypes progress with age, and sudden death is common in adults. Histology reveals myopathy. Homozygotes females are not able to deliver pups and homozygous males develop phimosis so do not breed.

Development

The hpbk mutation was identified in the great-granddaughter of an N-ethyl-N-nutrosourea (ENU) mutagenized C57BL/6J male in the Neuromutagenesis Facility at The Jackson Laboratory in 2001. A C57BL/6J male was treated with ENU and crossed to an untreated C57BL/6J female. The male offspring were bred with C57BL/6J females and their female offspring were backcrossed to their mutation-bearing father. The recessive mutations were revealed in the offspring and included one female with a humped spine. The ovaries of this mutant female were transplanted into a host and she was bred with a C57BL/6J male from which the heterozygous offspring were intercross to generate more humpback homozygotes. This mutant strain has been maintained by breeding the host of homozygous ovarian transplant with unaffected male siblings (heterozygotes or wild-type) and the heterozygous offspring are then sibling intercrossed.

Allele

Symbol: Notch3^hpbk
Name: humpback
MGI accession ID: MGI:4418503
Generation method: Chemically induced (ENU)
Marker symbol: Notch3
Marker name: notch 3
Marker synonyms: CADASIL; CADASIL1; CASIL; hpbk; IMF2; LMNS; N3
Chromosome: 17
Strain of origin: C57BL/6J
Molecular note: Exome sequencing of this ENU induced mutation revealed a G-to-A point mutation in Notch3, which disrupts the splice donor site at the exon 31-intron 31 boundary, changing it from G-GT to G-AT.