Mice homozygous for the fat spontaneous mutation (Cpefat) on a C57BLKS/J genetic background (N10) have a diabetes phenotype that is primarily restricted to males and is more severe than what is seen on the original HRS/J or C57BLKS/J (N5) genetic backgrounds. At weaning both males and female homozygous mutant mice were significantly lighter than wildtype or heterozygous littermates. Obesity develops between 6 and 8 weeks of age and mutant mice can be distinguished from wildtype littermates between 8 and 12 weeks of age. By 18 weeks fat mutant mice will reach 45-55 g and may reach 60-70 g by 6 months of age. Thus, the obesity is thus slower to develop than in the obese (Lepob) and diabetes (Leprdb) mutant mice. The excess adiposity is distributed throughout the body's fat stores, in contrast to the largely axial and inguinal fat deposition of the obese and diabetes mutant mice. Hyperinsulinemia is severe by 4 weeks of age and contin...
Mice homozygous for the fat spontaneous mutation (Cpefat) on a C57BLKS/J genetic background (N10) have a diabetes phenotype that is primarily restricted to males and is more severe than what is seen on the original HRS/J or C57BLKS/J (N5) genetic backgrounds. At weaning both males and female homozygous mutant mice were significantly lighter than wildtype or heterozygous littermates. Obesity develops between 6 and 8 weeks of age and mutant mice can be distinguished from wildtype littermates between 8 and 12 weeks of age. By 18 weeks fat mutant mice will reach 45-55 g and may reach 60-70 g by 6 months of age. Thus, the obesity is thus slower to develop than in the obese (Lepob) and diabetes (Leprdb) mutant mice. The excess adiposity is distributed throughout the body's fat stores, in contrast to the largely axial and inguinal fat deposition of the obese and diabetes mutant mice. Hyperinsulinemia is severe by 4 weeks of age and continues throughout life; it is associated with hypertrophy and hyperplasia of the islets of Langerhans. Male homozygotes backcrossed 10 generations to C57BLKS/J develop severe hyperglycemia after the development of gross obesity compared to a milder diabetic syndrome seen in males on a HRS/J or 5th generation backcross to C57BLKS. In contrast to obese and diabetes mutant mice on a C57BLKS background, glucose levels do not continue to rise but plateau around 400 - 600 mg/dL After 30 weeks of age plasma glucose levels of most male mutant mice are below 300 mg/dL despite continued weight gain and obesity. Most female mutant mice are resistant to development of hyperglycemia. Hyperglycemia is not associated with significant beta-cell necrosis or islet atrophy, occurs primarily in males. Homozygous fat mutant mice do not exhibit the hypercorticism characteristic of both obese and diabetes mutant mice. Proopiomelanocortin (POMC), the precursor of several neuroendocrine peptides that are ordinarily secreted in a regulated fashion, is misassorted to the constitutive secretory pathway in the pituitary intermediate lobe of fat mutant mice. Naggert et al. (1995) proposed that the obesity of fat homozygous mutant mice may reflect "defects in processing of prohormone forms of a variety of neuropeptides associated with the control of energy balance, nutrient partitioning and satiety.
The fat spontaneous mutation arose spontaneously on the HRS/J strain and was backcrossed 5 generations (N5) to C57BLKS/J by Drs. Coleman and Eicher. Backcrossing was later continued to N10 by Dr. Edward Leiter.
|Gene Symbol and Name||Cpe, carboxypeptidase E|
|Gene Synonym(s)||CARBE; CPH; Cph; Cph-1; Cph-1; Cph1; Cph1; NF-alpha1; R74677; carboxypeptidase H; carboxypeptidase H; expressed sequence R74677; fat; fat|
|Strain of Origin||HRS/J|
|Molecular Note||The molecular mutation responsible for the phenotype in the fat mouse is a T to C transition at nucleotide 729 of the mRNA. The codon of this nucleotide corresponds to amino acid 244 of the unprocessed preproenzyme or amino acid 202 of the mature peptidase. The mutation is predicted to alter a conserved serine to a proline residue in the encoded protein. Enzymatic activity of the mutant protein was shown to be abolished in fluorometric assays in vitro.|
This strain is maintained by mating heterozygous siblings as fat homozygous mutant mice are generally infertile. The genotype of progeny are determine by an allele specific PCR protocol (see Genetic Typing). Mice are maintained on a NIH-31 6% fat diet.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"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.
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.
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.
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.
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.