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PMID:11105903

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Citation

Morales, CR, Zhao, Q, El-Alfy, M and Suzuki, K Targeted disruption of the mouse prosaposin gene affects the development of the prostate gland and other male reproductive organs. J. Androl. 21:765-75

Abstract

The prosaposin gene encodes a 65-70 kilodalton (kd) protein, which is secreted or targeted to lysosomes. In lysosomes, prosaposin is the precursor of 4 activator proteins, designated saposins A, B, C, and D, which promote by acidic hydrolases, the degradation of glycosphingolipids with short oligosaccharide chains. Mutations of the prosaposin gene have been linked to several lysosomal storage disorders. An animal model was recently developed by creating a null allele in embryonic stem cells through gene targeting in order to investigate the phenotypic diversity of prosaposin mutations, the involvement of this protein in lysosomal storage diseases, and to develop potential therapeutic approaches. Mutant homozygous mice die at 35-40 days of age and neurological disorders contribute to their early death. Secreted prosaposin is present in milk and in cerebrospinal and seminal fluids. In the nervous system, prosaposin exhibits a trophic activity. Examination of reproduc-tive organs in homozygous mutant males shows several abnormalities such as a decrease in testis size with reduced spermiogenesis, and an involution of the prostate, seminal vesicle, and epididymis, although levels of testosterone in blood remain normal. In the prostate of homozygous mutants, only basal cells appear to be present, whereas secretory cells are absent. The epithelia in efferent ducts is formed by ciliated cells, whereas heterozygotes exhibit a majority of nonciliated cells. Our data indicate that prosaposin is involved in the development and maintenance of male reproductive organs. In prostatic epithelium, targeted disruption of the prosaposin gene appears to inactivate the mitogen-activated protein kinase pathway and to interfere with differentiation of secretory cells.

Links

PubMed

Keywords

Aging; Animals; Genitalia, Male/growth & development; Genitalia, Male/physiology; Glycoproteins/deficiency; Glycoproteins/genetics; Glycoproteins/physiology; Heterozygote; Homozygote; Male; Mice; Mice, Knockout; Prostate/cytology; Prostate/growth & development; Prostate/physiology; Protein Precursors/deficiency; Protein Precursors/genetics; Protein Precursors/metabolism; Saposins; Testis/cytology; Testis/growth & development; Testis/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ANDR

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SAP

involved_in

GO:0043408: regulation of MAPK cascade

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1888378

P

Seeded From UniProt

complete

MOUSE:SAP

involved_in

GO:0048589: developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1888378

P

Seeded From UniProt

complete

MOUSE:SAP

involved_in

GO:0060736: prostate gland growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1888378

P

Seeded From UniProt

complete

MOUSE:SAP

involved_in

GO:0060742: epithelial cell differentiation involved in prostate gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1888378

P

Seeded From UniProt

complete

MOUSE:ANDR

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:32290)
  • part_of:(CL:0000066)

Seeded From UniProt

complete


See also

References

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