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Generation and analysis of p23- and calnexin-deficient mice

Denzel, Angela; (1999) Generation and analysis of p23- and calnexin-deficient mice. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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This thesis provides in vivo information about two proteins - p23 and calnexin - which play major roles in the early secretory pathway of mammalian cells. The aim was to gain further understanding about the function of these proteins by generating mice deficient in the expression of p23 and calnexin. p23 is a member of the integral p24 protein family. These proteins are highly abundant in the endoplasmic reticulum and Golgi apparatus and are thought to play a role in protein transport and vesicle formation. Disruption of both p23 alleles results in early embryonic lethality. Inactivation of one allele leads not only to reduced levels of p23 itself but also of other family members. The reduction in steady state protein levels also leads to an altered subcellular distribution of p23 as well as p26 (another family member) in p23 heterozygous cells. In addition, structural changes in the Golgi apparatus, in particular dilated saccules, were observed. These changes in p23 heterozygous mice have functional consequences, resulting in specific defects in the secretion of some plasma proteins. Calnexin is a molecular chaperone molecule which is involved in the correct folding of newly synthesised polypeptide chains in the ER. 40% of the calnexin homozygous deficient mice died shortly after birth, the remaining 60% developed a severe neuronal phenotype and had to be sacrificed within 2 months. They were about one third smaller than their littermates and displayed motor disorders which included shaking of the body and a wobbly unsteady gait. Histological examination of brain, cerebellum, spinal cord, neuromuscular junctions and muscle did not reveal any abnormalities in the calnexin-deficient mice. Although these mice showed clear neurodegenerative symptoms, the molecular basis for the phenotype has not yet been characterised.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Generation and analysis of p23- and calnexin-deficient mice
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Calnexin
URI: https://discovery.ucl.ac.uk/id/eprint/10120403
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