129S/Sv-Ret^tm1Cos/J

Stock number: 009085
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Mice homozygous for the Ret^- allele harbor a knockout of the ret proto-oncogene locus and may be useful in studying kidney/urinary and peripheral nervous system development, as well as abnormal enteric neural crest cell migration and Hirschsprung's Disease.

Detailed description

The Ret^- allele (also called ret-k^-, ret-k minus, or c-ret^-) disrupts the region of the ret proto-oncogene (Ret; also called ret-k or c-ret) locus harboring the invariant lysine codon required for Ret kinase activity. Homozygous mice die around 16-24 hours after birth, exhibiting abnormalities in kidney/urinary (renal agenesis/hypodysplasia) and peripheral nervous system development (including sympathetic, parasympathetic, and enteric ganglia), as well as abnormal enteric neural crest cell migration. Because homozygous mice lack enteric ganglia from the hindgut, these mice are also a model of Hirschsprung's Disease.

Development

A targeting vector was designed to replace an 0.8 kb region of the ret proto-oncogene (Ret; also called ret-k or c-ret) locus, including the codon for an invariant lysine required for Ret kinase activity, with a neomycin resistance cassette. The construct was electroporated into 129S/SvEv-Gpi1^c derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with 129/SvEv mice to establish the colony. Heterozygous mice were bred with wildtype 129/SvEv (and/or 129S6/SvEvTac) mice for many generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred together 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.

Allele

Symbol: Ret^tm1Cos
Name: targeted mutation 1, Frank Costantini
MGI accession ID: MGI:2136894
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ret
Marker name: ret proto-oncogene
Chromosome: 6
Strain of origin: 129S/SvEv-Gpi1^c
Molecular note: A neomycin resistance cassette replaced 0.8 kb of sequence, including the codon for an invariant lysine required for kinase activity. Northern blot analysis did not detect normal transcripts in brains of homozygous mice, but did detect several transcripts with sizes consistent with predicted products of the mutant allele.