Overview

Homozygous M390R mutant Bbs1 (Bardet-Biedl syndrome 1 (human)) animals exhibit photoreceptor degeneration and severe obesity. Mice 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.

Donating Investigator

Val Sheffield, University of Iowa, HHMI

Genetic overview

Genetic Background	Generation

Bbs1^tm1Vcs

Allele Type	Gene Symbol	Gene Name
Targeted	Bbs1	Bardet-Biedl syndrome 1 (human)

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Research Applications

Diabetes and Obesity Research
Neurobiology Research
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

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 C57BL/6 by the donating laboratory.

Genetics

Bbs1^tm1Vcs

Allele Symbol: Bbs1^tm1Vcs

Allele Name	targeted mutation 1, Val C Sheffield
Allele Type	Targeted
Allele Synonym(s)	Bbs1^M390R
Gene Symbol and Name	Bbs1, Bardet-Biedl syndrome 1 (human)
Gene Synonym(s)
Promoter	Bbs1, Bardet-Biedl syndrome 1 (human), mouse, laboratory
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	19
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.
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 1

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Obesity Without Diabetes
Neurobiology Research
Reproductive Biology Research
- Fertility Defects
  - males only
- Developmental Defects Affecting Gonads
  - 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: Bbs1^tm1Vcs/Bbs1^tm1Vcs
involves: 129S1/Sv * 129X1/SvJ

adipose tissue phenotype

abnormal fat pad morphology
- increase in the amount of reproductive, perirenal, and omental fat

increased total body fat amount
- significant elevation in fat content at 3.5 and 6 months of age

increased brown adipose tissue amount

cellular phenotype

abnormal neuronal precursor proliferation
- 50% less in the periventricular region at P3 and P7
- Normal - however, lithium therapy rescues increased proliferation
- neuronal precursor cells are insensitive to PDGF-alpha treatment

absent sperm flagellum
- sperm lack flagella

abnormal ependyma motile cilium morphology
- ependymal cell cilia are either abnormally long (20%) or have swollen distal regions containing vesicular aggregates (80%)

increased neuron apoptosis
- 2-fold in the periventricular region at P3 and P7

growth/size/body region phenotype

obese

homeostasis/metabolism phenotype

increased circulating leptin level

mammalian phenotype

renal/urinary system phenotype
- Normal - unlike humans with Bardet-Biedl syndrome, mice do not develop renal cysts

limbs/digits/tail phenotype
- Normal - unlike humans with Bardet-Biedl syndrome, mice do not display polydactyly

nervous system phenotype
- Normal - motile cilia in the lateral ventricles are normal

mortality/aging
- Normal - unlike Bbs2, Bbs4, or Mkks homozygous null mice, no embryonic or neonatal lethality is seen

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%)

abnormal retinal photoreceptor morphology

increased neuron apoptosis
- 2-fold in the periventricular region at P3 and P7

enlarged lateral ventricles
- enlargement of the lateral ventricles can be detected by 3 weeks of age and increases with age
- enlargement of the lateral ventricles is more severe than that of the third ventricle
- ventriculomegaly restricted to the lateral and third cerebral ventricles

dilated brain ventricles
- dilated

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

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

abnormal neuronal precursor proliferation
- 50% less in the periventricular region at P3 and P7
- Normal - however, lithium therapy rescues increased proliferation
- neuronal precursor cells are insensitive to PDGF-alpha treatment

abnormal photoreceptor outer segment morphology
- at P21, retinas show protein mislocalization with a striking accumulation of Stx3 and Stxbp1 as well as loss of polarized Prom1 localization in the OS, similar to retinas in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes
- at P45, the lamellar structure of the OS is severely disrupted; abnormal vesicle formation and longitudinally oriented discs are observed similar to those in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

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

disorganized photoreceptor inner segment
- significant degeneration is seen at 6 months of age
- severe disruption and disorientation of outer segment membranous discs is seen

hydrocephaly
- non-obstructive
- Normal - however, lithium therapy rescues hydrocephalus

disorganized photoreceptor outer segment
- at P45, the OS structure is disorganized

enlarged third ventricle
- ventriculomegaly restricted to the lateral and third cerebral ventricles
- enlargement of the lateral ventricles is more severe than that of the third ventricle

photoreceptor inner segment degeneration
- significant degeneration is seen at 6 months of age

dilated lateral ventricles
- begins between P0 and P3

reproductive system phenotype

male infertility

absent sperm flagellum
- sperm lack flagella

taste/olfaction phenotype

impaired olfaction
- partial anosmia

behavior/neurological phenotype

hypoactivity

increased food intake

decreased aggression towards mice
- display a lack of social dominance

vision/eye phenotype

disorganized photoreceptor inner segment
- severe disruption and disorientation of outer segment membranous discs is seen
- significant degeneration is seen at 6 months of age

abnormal retinal photoreceptor morphology

abnormal cone electrophysiology
- the variance of the photopic b-wave is significantly different compared to controls

abnormal rod electrophysiology
- at 11 weeks of age significant attenuation is seen in a- and b-waves at high scotopic luminances
- Normal - however, at 11 weeks of age no difference is seen in amplitude or scotopic response at the lowest scotopic luminance

photoreceptor inner segment degeneration
- significant degeneration is seen at 6 months of age

abnormal photoreceptor outer segment morphology
- at P45, the lamellar structure of the OS is severely disrupted; abnormal vesicle formation and longitudinally oriented discs are observed similar to those in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes
- at P21, retinas show protein mislocalization with a striking accumulation of Stx3 and Stxbp1 as well as loss of polarized Prom1 localization in the OS, similar to retinas in Lztfl1^{tm1e(KOMP)Wtsi} homozygotes

disorganized photoreceptor outer segment
- at P45, the OS structure is disorganized

abnormal eye electrophysiology
- the c-wave amplitude is significantly reduced although the response is still luminance-graded

retinal outer nuclear layer degeneration
- significant degeneration is seen at 6 months of age

cardiovascular system phenotype

increased heart rate
- Normal - however, no significant changes in mean arterial pressure or cardiac size are detected
- higher heart rates in 3.5- to 6-month old mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Bbs1^tm1Vcs/Bbs1^tm1Vcs
B6.129-Bbs1

nervous system phenotype

decreased dendritic spine density
- Normal - however, dendritic length is not affected
- 10% reduction in total spine density of dentate gyrus neurons

References

Additional - Bbs1^tm1Vcs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Bbs1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, heterozygotes may be bred. Homozygous males are infertile due to lack of sperm flagella.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Bbs1^tm1Vcs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010726 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Bbs1<tm1Vcs>

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Frozen Mouse Embryo	B6.129-Bbs1<tm1Vcs>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Bbs1<tm1Vcs>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Bbs1<tm1Vcs>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Bbs1<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

Bbs1tm1Vcs

Allele Symbol: Bbs1tm1Vcs

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).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Bbs1tm1Vcs/Bbs1tm1Vcsinvolves: 129S1/Sv * 129X1/SvJ

adipose tissue phenotype

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

reproductive system phenotype

taste/olfaction phenotype

behavior/neurological phenotype

vision/eye phenotype

cardiovascular system phenotype

Genotype: Bbs1tm1Vcs/Bbs1tm1VcsB6.129-Bbs1

nervous system phenotype

References

Additional - Bbs1tm1Vcs 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

Bbs1^tm1Vcs

Allele Symbol: Bbs1^tm1Vcs

Genotype: Bbs1^tm1Vcs/Bbs1^tm1Vcs
involves: 129S1/Sv * 129X1/SvJ

Genotype: Bbs1^tm1Vcs/Bbs1^tm1Vcs
B6.129-Bbs1

Additional - Bbs1^tm1Vcs related