Description

Strain Information

Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote         (Female x Male)   27-DEC-12 Mating System Heterozygous x Noncarrier         (Female x Male)   27-DEC-12 Species laboratory mouse Generation +pN1+ (12-FEB-13) Generation Definitions   Donating Investigator Francis S. Collins,   NHGRI/NIH

Description
Mutations in the human LMNA gene cause Hutchinson-Gilford progeria syndrome, a rare autosomal dominant childhood disease that is characterized by features similar to premature aging, including progressive arteriosclerosis. These transgenic mice express the mutant human lamin A protein progerin, which carries a 50 amino acid C terminus region deletion, and results from the 1824C to T, G608G(encoded amino acid for codon 608 remains glycine), mis-sense mutation of the LMNA gene. Histological analysis of large arteries from hemizygous transgenic mice, beginning at 5 months of age, reveals progressive vascular smooth muscle cell loss, broken elastic fibers, thickened adventitia and medial layers, and proteoglycan and collagen accumulation in large arteries. Hemizygous transgenic mice older than 12 months exhibit calcification and severe vascular smooth muscle cell loss and extracellular matrix deposition of the large arteries. Mice hemizygous for the transgene display impaired blood pressure regulation with an abnormal response to the vasodilator, sodium nitroprusside. The progressive cardiovascular disease observed in transgenic mice recapitulates the cardiovascular pathology seen in human patients. The Donating Investigator reports that homozygous females are infertile and that a lower than expected number of homozygotes are born. For the first 4 months after birth, homozygotes exhibit a slower rate of weight gain when compared to hemizygotes. In addition to developing kyphosis, hair loss, tight skin, loss of subcutaneous fat and joint contracture, homozygotes develop a significantly more severe vascular damage with vascular smooth muscle depletion, calcification, and extremely thick adventitia. Homozygotes die at an average of 8 months of age.

Development
The 164.4 kb human BAC RP11-702H12 containing the entire LMNA gene, as well as the UBQLN4, MAPBPIP, and RAB25 genes was modified to insert the G608G HGPS mutation and a FRT site flanked kanamycin selection cassette into exon 11 of the LMNA gene. The kanamycin selection cassette was removed by transient Flp-recombinase expression. The resulting circular BAC transgene, which contains the G608G mutation in exon 11, and 109 extra nucleotides in intron 10 including an FRT site, EcoRI site, and SacI site, was microinjected into C57BL/6 donor eggs. Founder line H was subsequently established. The mice were maintained on the C57BL/6 background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

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

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Hutchinson-Gilford Progeria Syndrome; HGPS

- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Cardiomyopathy, Dilated, 1A; CMD1A   (LMNA) Cardiomyopathy, Dilated, with Hypergonadotropic Hypogonadism   (LMNA) Charcot-Marie-Tooth Disease, Axonal, Type 2B1; CMT2B1   (LMNA) Emery-Dreifuss Muscular Dystrophy 2, Autosomal Dominant; EDMD2   (LMNA) Heart-Hand Syndrome, Slovenian Type   (LMNA) Lipodystrophy, Familial Partial, Type 2; FPLD2   (LMNA) Mandibuloacral Dysplasia with Type A Lipodystrophy; MADA   (LMNA) Muscular Dystrophy, Congenital, Lmna-Related   (LMNA) Muscular Dystrophy, Limb-Girdle, Type 1B; LGMD1B   (LMNA) Restrictive Dermopathy, Lethal   (LMNA)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tg(LMNA*G608G)HClns/?

        C57BL/6-Tg(LMNA*G608G)HClns/J

• mortality/aging
• prenatal lethality
  • fewer homozygotes born than expected   (MGI Ref ID J:107176)
• cardiovascular system phenotype
• abnormal blood pressure regulation
  • impaired blood pressure regulation with an abnormal response to the vasodilator, sodium nitroprusside   (MGI Ref ID J:107176)
• abnormal vascular smooth muscle morphology
  • progressive vascular smooth muscle cell loss starting at 5 momnths of age   (MGI Ref ID J:107176)
  • broken elastic fibers, thickened adventitia and medial layers, and proteoglycan and collagen accumulation in large arteries.   (MGI Ref ID J:107176)
  • calcification and severe vascular smooth muscle cell loss and extracellular matrix deposition of the large arteries after 12 months of age   (MGI Ref ID J:107176)
• muscle phenotype
• abnormal vascular smooth muscle morphology
  • progressive vascular smooth muscle cell loss starting at 5 momnths of age   (MGI Ref ID J:107176)
  • broken elastic fibers, thickened adventitia and medial layers, and proteoglycan and collagen accumulation in large arteries.   (MGI Ref ID J:107176)
  • calcification and severe vascular smooth muscle cell loss and extracellular matrix deposition of the large arteries after 12 months of age   (MGI Ref ID J:107176)
• reproductive system phenotype
• female infertility
  • homozygous females are infertile   (MGI Ref ID J:107176)

View Research Applications

Research Applications

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

Cardiovascular Research
Vascular Defects

Research Tools
Cardiovascular Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(LMNA*G608G)HClns
Allele Name		transgene insertion H, Francis Collins
Allele Type		Transgenic (random, expressed)
Strain of Origin		C57BL/6
Expressed Gene		LMNA, lamin A/C, human
Promoter		LMNA, lamin A/C, human
Molecular Note		The 164.4 kb human BAC RP11-702H12 containing the entire LMNA gene, as well as the UBQLN4, MAPBPIP, and RAB25 genes was modified to insert the G608G HGPS mutation and a FRT site flanked kanamycin selection cassette into exon 11 of the LMNA gene. The kanamycin selection cassette was removed by transient Flp-recombinase expression. The resulting circular BAC transgene, which contains the G608G mutation in exon 11, and 109 extra nucleotides in intron 10 including an FRT site, EcoRI site, and SacI site, was microinjected into C57BL/6 donor eggs. Founder line H was subsequently established. [MGI Ref ID J:107176]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(LMNA*G608G)HClns,

SEPARATED MELT

Tg(LMNA*G608G)HClns, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Varga R; Eriksson M; Erdos MR; Olive M; Harten I; Kolodgie F; Capell BC; Cheng J; Faddah D; Perkins S; Avallone H; San H; Qu X; Ganesh S; Gordon LB; Virmani R; Wight TN; Nabel EG; Collins FS. 2006. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 103(9):3250-5. [PubMed: 16492728]  [MGI Ref ID J:107176]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, hemizygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). The Donating Investigator reports that homozygous females are infertile, a lower than expected number of homozygotes are born and that homozygotes die at an average age of 8 months.
Mating System	Noncarrier x Hemizygote         (Female x Male)   27-DEC-12
	Heterozygous x Noncarrier         (Female x Male)   27-DEC-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Use restrictions apply, see Policy on Licensing and Use Restrictions.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "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 the 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 or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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 and PRODUCTS 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.