STOCK Hsd17b4tm1Baes/Ph
| Status | Available to order |
| EMMA ID | EM:12344 |
| International strain name | STOCK Hsd17b4tm1Baes/Ph |
| Alternative name | SWR-MFP2 +/- |
| Strain type | Targeted Mutant Strains : Knock-out |
| Allele/Transgene symbol | Hsd17b4tm1Baes, |
| Gene/Transgene symbol | Hsd17b4 |
Information from provider
| Provider | Miriam Baes |
| Provider affiliation | Department of Pharmaceutical and Pharmacological, Cell Metabolism, Katholieke Universiteit Leuven |
| Genetic information | Hsd17b4 ((hydroxysteroid (17-beta) dehydrogenase 4) gene amplified from P1 genomic library (donor strain not known). Targeting vector DNA (for recombinant removal of exon 1-3 of the Hsd17b4 gene) was transfected into R1 ES cells ((129X1/SvJ x 129S1/Sv)F1); ES cells were transferred to Swiss background - not otherwise specified, first publications concerning the generated knock-out mice (e.g. in 2006) described the line as [Tac(Sw)fBR]SV129. After import of these mice to HMGU they were once crossed to Swiss animals (probably SWR/OlaHsd); after that, only sibling matings were performed, 35 times. |
| Phenotypic information | Homozygous:The first 3 exons of the mouse Hsd17b4 gene are removed by homologous recombination. As a result, no functional protein for MFP2 (Hsd17b4 or 17beta-HSD4) can be formed, and important central enzymatic reactions, such as e.g. beta-oxidation of certain fatty acids, can no longer take place. Homozygous MFP2 knock-out (MFP2 -/-) mice are born, but up to 30% of young MFP2 -/- mice can die prematurely after birth. The growth is delayed and the knock-out animals never reach the weight and size of wild-type or heterozygous siblings. Females show impaired fertility. Males develop complete testis atrophy. MFP2-deficient mice accumulate very long chain fatty acids (VLCFA) in the brain, C27 bile acid intermediates in the bile, and phospholipids and branched chain fatty acids in the liver, due to impaired peroxisomal beta-oxidation of these substrates. In the MFP2 knock-out brain, various anomalies can be detected, such as accumulation of neutral fats, overexpression of catalase and severe astro- and microgliosis. Some weeks after birth, the MFP2 knock-out mice show limb cramping when lifted on the tail. Further, the animals develop diminished motor skills, which in turn leads to less mobility. The homozygous animals of the SWR-MFP2 line die at the age of about 12 weeks.Heterozygous:The first 3 exons of the mouse Hsd17b4 gene are removed by homologous recombination. As a result, no functional protein for MFP2 (Hsd17b4 or 17beta-HSD4) can be formed, and important central enzymatic reactions, such as e.g. beta-oxidation of certain fatty acids, can no longer take place. However, heterozygous MFP2 knock-out (MFP2 +/-) mice do not show a phenotype since the Hsd17b14 gene in these animals is switched off on only one allele and the wild-type gene of the other allele takes full function in the mouse. |
| Breeding history | See genetic description above |
| References |
|
| Homozygous fertile | no |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Institute of Molecular Genetics, Prague, Czech Republic |
| Breeding at archiving centre | Heterozygous x wild-type mice |
| Stage of embryos | 2-cell |
Disease and phenotype information
MGI allele-associated human disease models
Orphanet associated rare diseases, based on orthologous gene matching
- Perrault syndrome / Orphanet_2855
- Bifunctional enzyme deficiency / Orphanet_300
Literature references
- Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids.;Baes M, Huyghe S, Carmeliet P, Declercq P E, Collen D, Mannaerts G P, Van Veldhoven P P, ;2000;The Journal of biological chemistry;275;16329-36; 10748062
- Peroxisomal multifunctional protein 2 is essential for lipid homeostasis in Sertoli cells and male fertility in mice.;Huyghe Steven, Schmalbruch Henning, De Gendt Karel, Verhoeven Guido, Guillou Florian, Van Veldhoven Paul P, Baes Myriam, ;2006;Endocrinology;147;2228-36; 16484321