Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Val Sheffield,   University of Iowa, HHMI

Description
Homozygous M390R mutant animals exhibit photoreceptor degeneration and severe obesity. By week 12, homozygous mutant mice are significantly heavier than wildtype or heterozygous mice. Animals are hyperphagic and hyperleptinemic with reduced locomotor activity but no elevation of mean arterial blood pressure. Lateral ventricles in the brain are enlarged and the corpus striatum is reduced. Males lack sperm flagella and are infertile. Although a model of Bardet-Biedl syndrome (BBS, these mice do not demonstrate polycactyly or renal cysts). Expression levels are comparable to those of wildtype mice as determined by Northern blot. Homozygotes are recovered at predicted Mendelian ratios from heterozygous crosses.

Development
A methionine to arginine (ATG to AGG) mutation was introduced at codon 390 (exon 12) and an in-frame neomycin resistance cassette was placed in intron 12 of the targeted gene. The (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cell line was used to create the mutation. This strain was backcrossed seven times to 129/SvEv by the donating laboratory.

Related Strains

Strains carrying   Bbs1^tm1Vcs allele

010726

B6.129-Bbs1tm1Vcs/J

View Strains carrying   Bbs1^tm1Vcs     (1 strain)

Strains carrying other alleles of Bbs1

010726

B6.129-Bbs1tm1Vcs/J

View Strains carrying other alleles of Bbs1     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Bardet-Biedl Syndrome; BBS - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Bbs1^tm1Vcs/Bbs1^tm1Vcs

        involves: 129S1/Sv * 129X1/SvJ

• mortality/aging
• *normal* mortality/aging
  • unlike Bbs2, Bbs4, or Mkks homozygous null mice, no embryonic or neonatal lethality is seen   (MGI Ref ID J:128532)
• reproductive system phenotype
• absent sperm flagellum
  • sperm lack flagella   (MGI Ref ID J:128532)
• male infertility   (MGI Ref ID J:128532)
• taste/olfaction phenotype
• impaired olfaction
  • partial anosmia   (MGI Ref ID J:128532)
• behavior/neurological phenotype
• decreased aggression towards mice
  • display a lack of social dominance   (MGI Ref ID J:128532)
• hypoactivity   (MGI Ref ID J:128532)
• increased eating behavior
  • increased food intake   (MGI Ref ID J:128532)
• growth/size phenotype
• obese   (MGI Ref ID J:128532)
• adipose tissue phenotype
• abnormal fat pad morphology
  • increase in the amount of reproductive, perirenal, and omental fat   (MGI Ref ID J:128532)
• increased brown adipose tissue amount   (MGI Ref ID J:128532)
• increased total body fat amount
  • significant elevation in fat content at 3.5 and 6 months of age   (MGI Ref ID J:128532)
• homeostasis/metabolism phenotype
• increased circulating leptin level   (MGI Ref ID J:128532)
• nervous system phenotype
• abnormal ependyma motile cilium morphology
  • ependymal cell cilia are either abnormally long (20%) or have swollen distal regions containing vesicular aggregates (80%)   (MGI Ref ID J:128532)
• abnormal retinal photoreceptor morphology   (MGI Ref ID J:128532)
• • disorganized photoreceptor inner segment
    • significant degeneration is seen at 6 months of age   (MGI Ref ID J:128532)
    • severe disruption and disorientation of outer segment membranous discs is seen   (MGI Ref ID J:128532)
  • photoreceptor inner segment degeneration
    • significant degeneration is seen at 6 months of age   (MGI Ref ID J:128532)
• abnormal striatum morphology
  • reduction in size of the corpus striatum at 3-weeks and 3.5- to 6-months of age   (MGI Ref ID J:128532)
• enlarged lateral ventricles
  • ventriculomegaly restricted to the lateral and third cerebral ventricles   (MGI Ref ID J:128532)
  • enlargement of the lateral ventricles can be detected by 3 weeks of age and increases with age   (MGI Ref ID J:128532)
  • enlargement of the lateral ventricles is more severe than that of the third ventricle   (MGI Ref ID J:128532)
• enlarged third ventricle
  • ventriculomegaly restricted to the lateral and third cerebral ventricles   (MGI Ref ID J:128532)
  • enlargement of the lateral ventricles is more severe than that of the third ventricle   (MGI Ref ID J:128532)
• small hippocampus
  • reduced in size at 3.5- to 6-months of age   (MGI Ref ID J:128532)
• thin cerebral cortex
  • thinning of the caudal half detected at 3.5- to 6-months of age   (MGI Ref ID J:128532)
• vision/eye phenotype
• abnormal eye electrophysiology
  • the c-wave amplitude is significantly reduced although the response is still luminance-graded   (MGI Ref ID J:128532)
• • abnormal cone electrophysiology
    • the variance of the photopic b-wave is significantly different compared to controls   (MGI Ref ID J:128532)
  • abnormal rod electrophysiology
    • at 11 weeks of age significant attenuation is seen in a- and b-waves at high scotopic luminances   (MGI Ref ID J:128532)
    • however, at 11 weeks of age no difference is seen in amplitude or scotopic response at the lowest scotopic luminance   (MGI Ref ID J:128532)
• abnormal retinal photoreceptor morphology   (MGI Ref ID J:128532)
• • disorganized photoreceptor inner segment
    • significant degeneration is seen at 6 months of age   (MGI Ref ID J:128532)
    • severe disruption and disorientation of outer segment membranous discs is seen   (MGI Ref ID J:128532)
  • photoreceptor inner segment degeneration
    • significant degeneration is seen at 6 months of age   (MGI Ref ID J:128532)
• retinal outer nuclear layer degeneration
  • significant degeneration is seen at 6 months of age   (MGI Ref ID J:128532)
• cardiovascular system phenotype
• increased heart rate
  • higher heart rates in 3.5- to 6-month old mice   (MGI Ref ID J:128532)
  • however, no significant changes in mean arterial pressure or cardiac size are detected   (MGI Ref ID J:128532)
• renal/urinary system phenotype
• *normal* renal/urinary system phenotype
  • unlike humans with Bardet-Biedl syndrome, mice do not develop renal cysts   (MGI Ref ID J:128532)
• limbs/digits/tail phenotype
• *normal* limbs/digits/tail phenotype
  • unlike humans with Bardet-Biedl syndrome, mice do not display polydactyly   (MGI Ref ID J:128532)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Obesity Without Diabetes

Neurobiology Research

Reproductive Biology Research
Developmental Defects Affecting Gonads
      males only
Fertility Defects
      males only

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bbs1tm1Vcs
Allele Name		targeted mutation 1, Val C Sheffield
Allele Type		Targeted (knock-in)
Common Name(s)		Bbs1M390R;
Mutation Made By		Val Sheffield,   University of Iowa, HHMI
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Bbs1, Bardet-Biedl syndrome 1 (human)
Chromosome		19
Gene Common Name(s)		AI451249; BBS2L2; D19Ertd609e; DNA segment, Chr 19, ERATO Doi 609, expressed; expressed sequence AI451249;
Molecular Note		The methionine codon (ATG) at position 390 in exon 12 was replaced with an arginine codon (AGG) and a neo cassette was inserted into intron 12 via homologous recombination. Northern blot analysis indicated that mRNA expression is not reduced in homozygous brains. [MGI Ref ID J:128532]

Genotyping

Genotyping Information

Genotyping Protocols

Bbs1^tm1Vcs, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Davis RE; Swiderski RE; Rahmouni K; Nishimura DY; Mullins RF; Agassandian K; Philp AR; Searby CC; Andrews MP; Thompson S; Berry CJ; Thedens DR; Yang B; Weiss RM; Cassell MD; Stone EM; Sheffield VC. 2007. A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Proc Natl Acad Sci U S A 104(49):19422-7. [PubMed: 18032602]  [MGI Ref ID J:128532]

Additional References

Bbs1^tm1Vcs related

Shah AS; Farmen SL; Moninger TO; Businga TR; Andrews MP; Bugge K; Searby CC; Nishimura D; Brogden KA; Kline JN; Sheffield VC; Welsh MJ. 2008. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc Natl Acad Sci U S A 105(9):3380-5. [PubMed: 18299575]  [MGI Ref ID J:132765]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygous males are infertile due to lack of sperm flagella.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

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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.

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