Overview

Also Known As:big giant head (bgh)

Mice homozygous for big giant head mutation (bgh; Spef2^bgh) have several abnormalities commonly associated with primary ciliary dyskinesia (PCD; including hydrocephalus, sinusitis and male infertility), as well as reduced respiratory ciliary motility. These C57BL/6J-congenic bgh mice (B6J.bgh) may be useful in studying PCD, as well as the role of mucociliary clearance in host defense.

Donating Investigator

Lance Lee, Sanford Children’s Health Research Center (Sanford Research Center)

Genetic overview

Genetic Background	Generation

Spef2^bgh

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU) (Null/Knockout)	Spef2	sperm flagellar 2

View Genetics

Research Applications

Developmental Biology Research
Cell Biology Research
Research Tools
Immunology, Inflammation and Autoimmunity Research
Reproductive Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

Mice homozygous for the "big giant head" mutation (bgh/bgh; Spef2^bgh/bgh) have several abnormalities commonly associated with primary ciliary dyskinesia (PCD); including hydrocephalus, sinusitis and male infertility. Homozygous mice do not exhibit situs inversus. Heterozygous mice are viable and fertile with no abnormal phenotype. The absence of full-length protein was confirmed by western blot analysis on testis extracts from homozygotes.

The donating investigator has assessed homozygous phenotype on three different backgrounds: C57BL/6J-congenic (B6J.bgh/bgh), 129S6/SvEvTac-congenic (129S6.bgh/bgh) and an F1 cross of these two backgrounds ((B6x129)F1.bgh/bgh). Overall, the severity of morphological brain damage is background strain-dependent. Alterations in astrocytosis, microglial activation, myelination, and the neuronal population were identified and are generally more severe on the C57BL/6J background. Specific details follow.

B6J.bgh/bgh mice exhibit lethal hydrocephalus (average death ~ 1 month of age) with damage to multiple cell types, as well as cilia-driven cerebrospinal fluid flow deficit, sinusitis and male infertility. B6J.bgh/bgh also exhibit upper airway abnormalities (reduced respiratory ciliary motility, but no ultrastructural defects); although no major cellular, developmental or inflammatory abnormalities in the lower airway are reported. The donating investigator reports that B6J.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice (B6J.bgh/+) are viable and fertile with no abnormal phenotype.

129S6.bgh/bgh mice do not develop gross hydrocephalus or exhibit early mortality, although they have cilia-driven cerebrospinal fluid flow deficits and variable levels of ventricular enlargement and brain damage. The sinusitis phenotype and male fertility phenotype for 129S6.bgh/bgh mice has not been characterized to date (although the donating investigator expects it to be similar to B6J.bgh/bgh animals). The specific upper airway vs. lower airway phenotype described for B6J.bgh/bgh has not been tested in 129S6.bgh/bgh to date (July 2015). The donating investigator reports that 129S6.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice (129S6.bgh/+) are viable and fertile with no abnormal phenotype.

(B6x129)F1.bgh/bgh mice exhibit sinusitis and male infertility, but no evidence of gross hydrocephalus or early mortality. (B6x129)F1.bgh/bgh also exhibit upper airway abnormalities (reduced respiratory ciliary motility, but no ultrastructural defects); although no major cellular, developmental or inflammatory abnormalities in the lower airway are reported. The infertility in (B6x129)F1.bgh/bgh males results from reduction in the number of elongating spermatids during spermiogenesis and structural defects in sperm flagella (this could not be tested directly in B6J.bgh/bgh males because they die before sexual maturity). The donating investigator reports that (B6x129)F1.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice ((B6x129)F1.bgh/+) are viable and fertile with no abnormal phenotype. Compared to similarly treated (B6x129)F1 wildtype mice, the (B6x129)F1.bgh/bgh mice show increased lymphocytic response when challenged with Streptococcus pneumonia infection.

Development

Dr. Richard J. Cornall (Oxford University) used N-ethyl-N-nitrosourea (ENU) mutagenesis in C57BL/6J mice to generate the fragile red (fred) mutant mice (Steap3^Y288H or Steap3^fred). The fred mice were next sent to Dr. Mark Fleming (Boston Children's Hospital). While maintaining them on a mixed C57BL/6J;C57BL/10J (B6;B10) background, some of offspring were found to spontaneously develop severe hydrocephalus. This resulting autosomal recessive "big giant head" mutation (bgh) was linked to two point mutations in the sperm flagellar 2 locus (Spef2) on chromosome 15: exon 3 has a T-to-A transversion (T835A) encoding a lysine-to-glutamine missense mutation (K412Q) in the DUF domain, and exon 28 has a C-to-G transversion (C8765G) encoding a lysine-to-nonsense codon mutation (K1320X). Both mutations are inherited in cis, and it is not known which mutation is causative in protein absence.
The Spef2^bgh mice were then backcrossed several generations with C57BL/6J inbred mice and 129S6/SvEvTac inbred mice; creating the individual B6J-congenic Spef2^bgh colony (B6J.bgh) and 129S6-congenic Spef2^bgh colony (129S6.bgh), respectively. In 2010, the B6J.bgh mice (backcrossed six generations onto C57BL/6J) were sent to Dr. Lance Lee (Sanford Research Center) for further analysis. There, Dr. Lee backcrossed the B6J.bgh colony six more generations onto C57BL/6J before sending black male mice to The Jackson Laboratory Repository in 2015.
Upon arrival, males were used to cryopreserve sperm. To establish our living B6J-congenic Spef2^bgh mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Finn R; Evans CC; Lee L. 2014. Strain-dependent brain defects in mouse models of primary ciliary dyskinesia with mutations in Pcdp1 and Spef2. Neuroscience 277:552-67PubMed: 25073043 MGI: J:215782
Sironen A; Kotaja N; Mulhern H; Wyatt TA; Sisson JH; Pavlik JA; Miiluniemi M; Fleming MD; Lee L. 2011. Loss of SPEF2 Function in Mice Results in Spermatogenesis Defects and Primary Ciliary Dyskinesia. Biol Reprod 85(4):690-701PubMed: 21715716 MGI: J:176695

View All References

Genetics

Spef2^bgh

Allele Symbol: Spef2^bgh

Allele Name	big giant head
Allele Type	Chemically induced (ENU) (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Spef2, sperm flagellar 2
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	15
Molecular Note	ENU induced a missense mutation in exon 3 that results in the amino acid substitution of lysine for glutamine in the DUF domain. An additional nonsense mutation in exon 28 results in a protein truncation after amino acid 1320. The absence of full-length protein was confirmed by western blot analysis on testis extracts.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

primary ciliary dyskinesia

Research Areas By Phenotype

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

Developmental Biology Research
- Skeletal Defects
  - hydrocephaly
- Cell Motility Defects
  - situs inversus
- Internal/Organ Defects
  - situs inversus
  - lung
- Perinatal Lethality
  - Homozygous
- Craniofacial and Palate Defects
  - hydrocephaly: severely abnormal skull
Cell Biology Research
- Cell Motility Defects
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - genes regulating susceptibility to infectious disease and endotoxin
- Infectious Disease
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
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: Spef2^bgh/Spef2^bgh
involves: C57BL/6J * C57BL/10J

cellular phenotype

abnormal respiratory motile cilium physiology
- the beat frequency of tracheal epithelial cilia is less than in wild-type mice

reproductive system phenotype

male infertility

respiratory system phenotype

abnormal respiratory motile cilium physiology
- the beat frequency of tracheal epithelial cilia is less than in wild-type mice

skeleton phenotype

enlarged neurocranium
- enlarged indicating ventricular dilatation

craniofacial phenotype

enlarged neurocranium
- enlarged indicating ventricular dilatation

mammalian phenotype

reproductive system phenotype
- Normal - female mice are fertile

mortality/aging

postnatal lethality, incomplete penetrance
- Background Sensitivity - some mice a few days after birth or within 1 week due to severe hydrocephalus unlike mice on a mixed background

premature death
- Background Sensitivity - average age of death is 24.5 days unlike mice on a mixed background

nervous system phenotype

abnormal brain morphology
- extensive ependymal cell sloughing in the underlying white layer
- Normal - however, ependymal cell cilia exhibit normal morphology

dilated lateral ventricles

gliosis
- in the underlying white layer

hydrocephaly

increased brain weight
- 2.2 times greater

Genotype: Spef2^bgh/Spef2^bgh
involves: 129S6/SvEvTac * C57BL/6J * C57BL/10J

cellular phenotype

abnormal respiratory motile cilium physiology
- the beat frequency of tracheal epithelial cilia is less than in wild-type mice

abnormal sperm axoneme morphology

abnormal sperm flagellum morphology
- short and disorganized

oligozoospermia
- very few mature sperm are present in the cauda epididymis

short sperm flagellum

reproductive system phenotype

abnormal sperm axoneme morphology

abnormal sperm flagellum morphology
- short and disorganized

abnormal spermatogenesis
- fibrous sheath formation is defective
- Normal - however, acrosome formation is normal
- mice exhibit a reduction in the number of elongating spermatids in the stage II-V tubules
- mitochondria are either absent from the sperm tail or are highly disorganized

male infertility

oligozoospermia
- very few mature sperm are present in the cauda epididymis

short sperm flagellum

respiratory system phenotype

abnormal respiratory motile cilium physiology
- the beat frequency of tracheal epithelial cilia is less than in wild-type mice

sinus inflammation

immune system phenotype

sinus inflammation

mammalian phenotype

mortality/aging
- Background Sensitivity - mice exhibit no early mortality unlike on a background lacking 129S6/SvEvTac

nervous system phenotype
- Background Sensitivity - mice do not exhibit evidence of gross hydrocephalus unlike on a background lacking 129S6/SvEvTac

reproductive system phenotype
- Normal - female mice are fertile

References

Finn R; Evans CC; Lee L. 2014. Strain-dependent brain defects in mouse models of primary ciliary dyskinesia with mutations in Pcdp1 and Spef2. Neuroscience 277:552-67PubMed: 25073043 MGI: J:215782
Sironen A; Kotaja N; Mulhern H; Wyatt TA; Sisson JH; Pavlik JA; Miiluniemi M; Fleming MD; Lee L. 2011. Loss of SPEF2 Function in Mice Results in Spermatogenesis Defects and Primary Ciliary Dyskinesia. Biol Reprod 85(4):690-701PubMed: 21715716 MGI: J:176695

Additional - Spef2^bgh related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Spef2
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygous mice on the C57BL/6J genetic background (B6J.bgh/bgh) exhibit lethal hydrocephalus (average death ~ 1 month of age) and male infertility. Therefore, when maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the big giant head (bgh) mouse strain in a publication, please cite the originating article(s) and include JAX stock #027799 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 Spef2<bgh>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:big giant head (bgh)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Spef2bgh

Allele Symbol: Spef2bgh

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Spef2bgh/Spef2bghinvolves: C57BL/6J * C57BL/10J

cellular phenotype

reproductive system phenotype

respiratory system phenotype

skeleton phenotype

craniofacial phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

Genotype: Spef2bgh/Spef2bghinvolves: 129S6/SvEvTac * C57BL/6J * C57BL/10J

cellular phenotype

reproductive system phenotype

respiratory system phenotype

immune system phenotype

mammalian phenotype

References

Additional - Spef2bgh related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Spef2^bgh

Allele Symbol: Spef2^bgh

Genotype: Spef2^bgh/Spef2^bgh
involves: C57BL/6J * C57BL/10J

Genotype: Spef2^bgh/Spef2^bgh
involves: 129S6/SvEvTac * C57BL/6J * C57BL/10J

Additional - Spef2^bgh related