B6.129-Mkks^tm1Vcs/J

Stock number: 014607
Research areas: Developmental Biology Research, Diabetes and Obesity Research, Mouse/Human Gene Homologs, Reproductive Biology Research

Description

In this strain a neomycin (neo) resistance cassette replaces exon 3 of the McKusick-Kaufman syndrome protein (Mkks or Bbs6) gene, abolishing gene function. These mice may be useful for studying the pathophysiology of McKusick-Kaufman syndrome and Bardet-Biedl syndrome.

Detailed description

In this strain a neomycin (neo) resistance cassette replaces exon 3 of the McKusick-Kaufman syndrome protein (Mkks or Bbs6) gene, abolishing gene function. Homozygous females are viable and fertile, while homozygous males are infertile due to lack of flagellated sperm. These mice are also smaller at birth than littermates. Mutations in Mkks have been known to cause McKusick-Kaufman syndrome (MKS) and Bardet-Biedl syndrome (BBS). MKS is a disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, while BBS is a pleiotropic disorder characterized by retinal and photoreceptor degeneration, obesity, polydactyly, renal abnormalities, hypogenitalism and cognitive impairment. Mkks^-/- mice lack MKKS expression in brain, lung, heart, kidney, eye, liver, spleen, testes, and muscle. They develop age-related blindness due to retinal degeneration, are obese, and have elevated blood pressure. These mice may be useful for studying the pathophysiology of MKS and BBS.

Development

A targeting vector was designed to replace exon 3 of the McKusick-Kaufman syndrome protein (Mkks) gene with a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6J mice. The donating investigator reported that these mice were then backcrossed at least six generations to a C57BL/6 background (see SNP note below). Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. At least 1 marker, on Chromosome 9, is segregating, suggesting an incomplete backcross.

Allele

Symbol: Mkks^tm1Vcs
Name: targeted mutation 1, Val C Sheffield
MGI accession ID: MGI:3526444
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Mkks^-; Bbs6^-
Marker symbol: Mkks
Marker name: McKusick-Kaufman syndrome
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A targeting construct was designed to replace exon 3 with a neo. Northern blot of mutants confirmed absence of mRNA in kidneys.