Overview

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.

Donating Investigator

Val Sheffield, University of Iowa, HHMI

Genetic overview

Genetic Background	Generation

Mkks^tm1Vcs

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Mkks	McKusick-Kaufman syndrome

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Research Applications

Diabetes and Obesity Research
Developmental Biology Research
Mouse/Human Gene Homologs
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Fath MA; Mullins RF; Searby C; Nishimura DY; Wei J; Rahmouni K; Davis RE; Tayeh MK; Andrews M; Yang B; Sigmund CD; Stone EM; Sheffield VC. 2005. Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum Mol Genet 14(9):1109-18PubMed: 15772095 MGI: J:99276

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Genetics

Mkks^tm1Vcs

Allele Symbol: Mkks^tm1Vcs

Allele Name	targeted mutation 1, Val C Sheffield
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Bbs6^-; Mkks^-
Gene Symbol and Name	Mkks, McKusick-Kaufman syndrome
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	2
Molecular Note	A targeting construct was designed to replace exon 3 with a neo. Northern blot of mutants confirmed absence of mRNA in kidneys.
Mutations Made By	Val Sheffield, University of Iowa, HHMI

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Bardet-Biedl syndrome 6

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

obesity

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Developmental Biology Research
- Eye Defects
Mouse/Human Gene Homologs
- retinal degeneration, slow
Reproductive Biology Research
- Fertility Defects
  - males only

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mkks^tm1Vcs/Mkks^tm1Vcs
involves: 129S1/Sv * 129X1/SvJ

nervous system phenotype

enlarged third ventricle
- enlarged at 3.5- to 6-months of age

enlarged lateral ventricles
- enlarged at 3.5- to 6-months of age

decreased striatum size
- reduction in size of the corpus striatum at 3-weeks and 3.5- to 6-months of age

thin cerebral cortex
- thinning of the caudal half detected at 3.5- to 6-months of age

small hippocampus
- reduced in size at 3.5- to 6-months of age

Genotype: Mkks^tm1Vcs/Mkks^tm1Vcs
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

mortality/aging

prenatal lethality, incomplete penetrance
- the proportion of homozygotes is decreased to 19.1% and data suggest death late in gestation

reproductive system phenotype

absent sperm flagellum
- spermatozoa lack flagella but have normally formed heads and cilia on epithelial cells form normally

male infertility

taste/olfaction phenotype

abnormal olfaction
- decreased olfactory ability suggested by a decreased ability to find hidden food

vision/eye phenotype

retinal degeneration
- at 8 months of age the outer nuclear layer is completely degenerated and no remnants of the inner or outer segments are seen
- at 2-3 months of age a slight reduction in the outer nuclear layer and some cell nuclei in the subretinal space were seen

behavior/neurological phenotype

hypoactivity
- 24 hour telemetry indicates a significant decrease in activity; however, no significant differences in muscle or motor neuron function dependent behaviors are seen

decreased aggression
- homozygotes are more docile during handling and in 72% and 76% of trials were submissive to wild-type and heterozygous mice, respectively

decreased vocalization
- females are less vocal during handling

cardiovascular system phenotype

increased systemic arterial blood pressure
- diastolic, systolic, and mean blood pressure are increased with mean arterial pressure increased on average by 12 mmHg

cellular phenotype

absent sperm flagellum
- spermatozoa lack flagella but have normally formed heads and cilia on epithelial cells form normally

growth/size/body region phenotype

obese
- by 28 weeks of age homozygotes weigh significantly more than wild-type or heterozygous littermates and the weight difference is greater in females than in males

decreased body weight
- at weaning homozygotes weigh significantly less than wild-type or heterozygous littermates

homeostasis/metabolism phenotype

increased circulating leptin level

mammalian phenotype

limbs/digits/tail phenotype
- Normal - no polydactyly or other notable limb malformations are seen

References

Fath MA; Mullins RF; Searby C; Nishimura DY; Wei J; Rahmouni K; Davis RE; Tayeh MK; Andrews M; Yang B; Sigmund CD; Stone EM; Sheffield VC. 2005. Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum Mol Genet 14(9):1109-18PubMed: 15772095 MGI: J:99276

Additional - Mkks^tm1Vcs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together. Homozygous males are infertile due to obesity and lack of flagellated sperm. These mice are also smaller at birth than littermates.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Mkks^tm1Vcs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014607 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or wildtype for Mkks<tm1Vcs>

Related Products and Services

Frozen Mouse Embryo	B6.129-Mkks<tm1Vcs>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Mkks<tm1Vcs>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Mkks<tm1Vcs>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Mkks<tm1Vcs>/J Frozen Embryo	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Mkkstm1Vcs

Allele Symbol: Mkkstm1Vcs

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Mkkstm1Vcs/Mkkstm1Vcsinvolves: 129S1/Sv * 129X1/SvJ

nervous system phenotype

Genotype: Mkkstm1Vcs/Mkkstm1Vcseither: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

mortality/aging

reproductive system phenotype

taste/olfaction phenotype

vision/eye phenotype

behavior/neurological phenotype

cardiovascular system phenotype

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mammalian phenotype

References

Additional - Mkkstm1Vcs related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Mkks^tm1Vcs

Allele Symbol: Mkks^tm1Vcs

Genotype: Mkks^tm1Vcs/Mkks^tm1Vcs
involves: 129S1/Sv * 129X1/SvJ

Genotype: Mkks^tm1Vcs/Mkks^tm1Vcs
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6J)

Additional - Mkks^tm1Vcs related