Overview

These "7B2" mutant mice may be useful in studies of corticosterone excess and its profound developmental effects, Cushing's disease, and other neuro-endocrine, obesity, or metabolism research. However, it should be noted that the phenotype of the 7B2-null mice on a mixed 129S genetic background distributed by The Jackson Laboratory Repository could vary from that originally described for 7B2-null mice with a different 129S genetic background.

Donating Investigator

Iris Lindberg, University of Maryland, Baltimore

Genetic overview

Genetic Background	Generation

Scg5^tm1Led

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Scg5	secretogranin V

View Genetics

Research Applications

Endocrine Deficiency Research
Diabetes and Obesity Research
Research Tools
Cardiovascular Research
Metabolism Research
Internal/Organ Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Important Note

The colony at The Jackson Laboratory Repository is on a mixed 129S genetic background and may not recapitulate the phenotype originally described for mutant mice with a different 129S genetic background.

Detailed Description

The colony at The Jackson Laboratory Repository is on a mixed 129S genetic background and may not recapitulate the phenotype originally described.

The following text reflects the phenotype reported by the donating investigator (Dr. Iris Lindberg) on a "129Sv" genetic background (probably "Taconic Sv129" (129S6/SvEvJ)).

While heterozygotes are viable and fertile, mice homozygous for this mutation (7B2-null) die in prepubertal or pubertal ages (5 weeks) with severe cardio-respiratory failure, convulsions, and hypothermia. No transcripts are detected in brain tissue from the targeted gene. 7B2-null mice are unable to make an active form of prohormone convertase 2 (PC2) and have high circulating corticosterone. Homozygotes on the "129Sv" genetic background exhibit Cushing's-like disease pathologies of liver, pancreas, and pituitary; including pituitary-dependent hyperadrenocorticosteronism, severe hypoglycemia, hyperproinsulinemia, adrenal hypertrophy, pituitary hypotrophy, and altered islet cell morphology. 7B2-null mice develop the disease from intermediate lobe ACTH hypersecretion (rather than from pituitary adenomas). Other abnormalities include thinning fur, thin tail, skeletal defects, dorsal and intraperitoneal adipose deposits, low blood sugar, fatty liver, and inability to synthesize glucagon. The donating investigator reports that null pups on the 129/SvEv genetic background are distinguishable by appearance, do not compete well for milk, and suggests thinning litters to 1-2 mice to obtain homozygotes.

In 2008, 7B2-null mice on the mixed 129S genetic background were sent from The Jackson Laboratory Repository colony back to the donating investigator (Dr. Iris Lindberg; now at University of Maryland). In November 2010, Dr. Lindberg reported that 7B2-null mice no longer exhibit the lethal phenotype observed for 7B2-null mice on a "129Sv" genetic background (probably "Taconic Sv129" (129S6/SvEvJ)). The cause of this is not known; but may be due to 129 substrain differences and/or husbandry changes in different vivaria, or other. In addition, Dr. Lindberg backcrossed the mice onto "the Taconic 129Sv background" for eight generations and was unable to recapitulate the homozygous lethal phenotype. Therefore, the 7B2-null mice on the mixed 129S genetic background distributed from The Jackson Laboratory Repository may no longer represent a Cushing's disease model.

These 7B2-null mice may be useful in studies of corticosterone excess and its profound developmental effects, Cushing's disease, and other neuro-endocrine, obesity, or metabolism research. However, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A transposon-based gene targeting approach was designed to interrupt exon 3 of the targeted gene by random integration of a transposon and subsequent introduction of a neo cassette. The construct was electroporated into 129/SvEv embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric males were crossed with 129/SvEv females. Heterozygous mice on this 129/SvEv genetic background were bred together for many generations prior to arrival at The Jackson Laboratory Repository. Upon arrival, mutant mice were bred with 129S1/SvImJ (Stock No. 002448) for at least one generation to rederive and establish the Jackson Laboratory Repository colony. After this, sperm from heterozygous males was cryopreserved.

Control Suggestions

Wild-type from the colony

Approximate Controls

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Westphal CH; Muller L; Zhou A; Zhu X; Bonner-Weir S; Schambelan M; Steiner DF; Lindberg I; Leder P. 1999. The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease. Cell 96(5):689-700PubMed: 10089884 MGI: J:53349
Sarac MS; Zieske AW; Lindberg I. 2002. The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities. Endocrinology 143(6):2324-32PubMed: 12021197 MGI: J:77510

View All References

Genetics

Scg5^tm1Led

Allele Symbol: Scg5^tm1Led

Allele Name	targeted mutation 1, Philip Leder
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Philip Leder; Scg5^tm1Led
Gene Symbol and Name	Scg5, secretogranin V
Gene Synonym(s)	expressed sequence AI325031; AI325031; Sgne1; 7B2; P7B2; Sgne-1; Sgne-1; SgV; secretory granule neuroendocrine protein 1, 7B2 protein; SGNE1; Sgne1
Strain of Origin	129S6/SvEvTac
Chromosome	2
General Note	Unlike classical Cushing's disease, which results from excess ACTH secretion from pituitary adenomas, null mice develop this disease from intermediate lobe ACTH hypersecretion. (J:77510)
Molecular Note	Insertion of a neomycin resistance cassette placed an artificial transposon after the eightieth base pair of exon 3 and disrupted the gene. Northern analysis of brain did not detect transcript in homozygous mice.
Mutations Made By	Dr. Philip Leder, Harvard Medical School

Disease/Phenotype

Disease Terms

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

pituitary-dependent Cushing's disease

Research Areas By Phenotype

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

Endocrine Deficiency Research
- Hypothalamus/Pituitary Defects
- Adrenal Cortex Defects
- Adrenal Medulla Defects
Diabetes and Obesity Research
- Hypoglycemia
- Hyperinsulinemia
Research Tools
- Cardiovascular Research
- Diabetes and Obesity Research
- Internal/Organ Research
- Endocrine Deficiency Research
- Metabolism Research
Cardiovascular Research
- Other
  - altered fat metabolism
Metabolism Research
- Lipid Metabolism
Internal/Organ Research
- Adrenal Cortex Defects
- Adrenal Medulla Defects
Developmental Biology Research
- Perinatal Lethality
  - Homozygous

Mammalian Phenotype Terms by Genotype

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

Genotype: Scg5^tm1Led/Scg5^tm1Led
either: 129S6/SvEvTac or (involves: 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6)

adipose tissue phenotype

abnormal adipose tissue distribution
- retroperitoneal fat deposits
- surviving mice show abnormal fat deposition on the back and around the neck

cellular phenotype

hepatic necrosis

endocrine/exocrine gland phenotype

abnormal adrenal gland morphology

abnormal gland morphology

abnormal pancreatic islet morphology
- increased beta and non-beta endocrine cell mass in the pancreas

adrenal cortical hyperplasia

cryptorchism
- undescended testes frequently

increased pancreatic beta cell mass

pancreatic islet hyperplasia
- architecture of the islets is disrupted

small adenohypophysis
- hypotrophy of the anterior pituitary

growth/size/body region phenotype

decreased body size
- severely runted at 4-5 weeks of age

hematopoietic system phenotype

spleen atrophy
- part of a generalized lymphoid atrophy
- spleen was 1/5 normal size with an abnormal architecture

homeostasis/metabolism phenotype

abnormal circulating insulin level
- delayed conversion of proinsulin I and II with increased proinsulin levels
- increased circulating levels of insulin-like material

abnormal glucose homeostasis
- high levels of free tissue glucose in the liver and decreased free glucose in muscle

abnormal mineral level
- levels are significantly decreased in heart while liver and brain levels are increased 2X

decreased body temperature
- hypothermia occurs in the hours just before death

decreased circulating glucagon level
- mature glucagons are eliminated and only limited levels of intermediate products are found

decreased circulating magnesium level
- levels are significantly decreased in plasma

hypoglycemia

increased adrenocorticotropin level
- levels were increased 10-20% in the pituitary

increased circulating corticosterone level
- 4X increase in serum corticosterone

increased circulating lactate level
- increased lactate levels in plasma

increased liver glycogen level
- liver glycogen levels increased 5X

behavior/neurological phenotype

convulsive seizures
- convulsions occur just before death

polyphagia

immune system phenotype

spleen atrophy
- part of a generalized lymphoid atrophy
- spleen was 1/5 normal size with an abnormal architecture

integument phenotype

abnormal hair growth

alopecia
- regional hair loss

ecchymosis
- mice are often ecchymotic

hyperkeratosis

pallor
- mice are pale

sparse hair

thin dermal layer
- dermal atrophy

thin skin
- thinning skin

liver/biliary system phenotype

enlarged liver
- significant hepatomegaly

hepatic necrosis

hepatic steatosis
- severe fat vacuolation and abnormal liver architecture
- yellow color to liver

increased liver glycogen level
- liver glycogen levels increased 5X

cardiovascular system phenotype

abnormal cardiovascular system morphology

bruising
- mice are often easily bruised

dystrophic cardiac calcinosis

ecchymosis
- mice are often ecchymotic

enlarged heart

hemorrhage
- often significant bleeding into the abdomen

hemothorax

mortality/aging

postnatal lethality, incomplete penetrance
- only about 11% survive to weaning

nervous system phenotype

convulsive seizures
- convulsions occur just before death

small adenohypophysis
- hypotrophy of the anterior pituitary

reproductive system phenotype

cryptorchism
- undescended testes frequently

respiratory system phenotype

abnormal respiration

hemothorax

respiratory distress
- experience shortness of breath just before death
- mice suffer from labored respiration in the last day before dying

References

Westphal CH; Muller L; Zhou A; Zhu X; Bonner-Weir S; Schambelan M; Steiner DF; Lindberg I; Leder P. 1999. The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease. Cell 96(5):689-700PubMed: 10089884 MGI: J:53349
Sarac MS; Zieske AW; Lindberg I. 2002. The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities. Endocrinology 143(6):2324-32PubMed: 12021197 MGI: J:77510

Additional - Scg5^tm1Led related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Scg5
- Standard PCR:Generic Neo
- Probe:Generic Neo
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygotes. These mice are on a mixed 129S genetic background. The published phenotype of homozygous mice (on a "129Sv" genetic background (probably "Taconic Sv129" (129S6/SvEvJ)) die around 5 weeks of age. The donating investigator reports that null pups are distinguishable by appearance, do not compete well for milk, and suggests thinning litters to 1-2 mice to obtain homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the 129S-Scg5^tm1Led/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007005 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 Wild-type for Scg5<tm1Led>

Related Products and Services

Frozen Mouse Embryo	129S-Scg5<tm1Led>/J	$2595.00
Frozen Mouse Embryo	129S-Scg5<tm1Led>/J	$2595.00
Frozen Mouse Embryo	129S-Scg5<tm1Led>/J	$3373.50
Frozen Mouse Embryo	129S-Scg5<tm1Led>/J	$3373.50

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.

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

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.

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Scg5tm1Led

Allele Symbol: Scg5tm1Led

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: Scg5tm1Led/Scg5tm1Ledeither: 129S6/SvEvTac or (involves: 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6)

adipose tissue phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

cardiovascular system phenotype

mortality/aging

nervous system phenotype

reproductive system phenotype

respiratory system phenotype

References

Additional - Scg5tm1Led 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Scg5^tm1Led

Allele Symbol: Scg5^tm1Led

Genotype: Scg5^tm1Led/Scg5^tm1Led
either: 129S6/SvEvTac or (involves: 129S6/SvEvTac * FVB) or (involves: 129S6/SvEvTac * C57BL/6)

Additional - Scg5^tm1Led related