Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia

Ying Ming Kuo, Jacque L. Duncan, Shawn Westaway, Haidong Yang, George Nune, Eugene Yujun Xu, Susan Hayflick, Jane Gitschier

Research output: Contribution to journalArticle

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Abstract

Pantothenate kinase-associated neurodegeneration (PKAN, formerly known as Hallervorden-Spatz syndrome) is a rare but devastating neurodegenerative disorder, resulting from an inherited defect in coenzyme A biosynthesis. As pathology in the human condition is limited to the central nervous system, specifically the retina and globus pallidus, we have generated a mouse knock-out of the orthologous murine gene (Pank2) to enhance our understanding of the mechanisms of disease and to serve as a testing ground for therapies. Over time, the homozygous null mice manifest retinal degeneration, as evidenced by electroretinography, light microscopy and pupillometry response. Specifically, Pank2 mice show progressive photoreceptor decline, with significantly lower scotopic a- and b-wave amplitudes, decreased cell number and disruption of the outer segment and reduced pupillary constriction response when compared with those of wild-type littermates. Additionally, the homozygous male mutants are infertile due to azoospermia, a condition that was not appreciated in the human. Arrest occurs in spermiogenesis, with complete absence of elongated and mature spermatids. In contrast to the human, however, no changes were observed in the basal ganglia by MRI or by histological exam, nor were there signs of dystonia, even after following the mice for one year. Pank2 mice are 20% decreased in weight when compared with their wild-type littermates; however, dysphagia was not apparent. Immunohistochemistry shows staining consistent with localization of Pank2 to the mitochondria in both the retina and the spermatozoa.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalHuman Molecular Genetics
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2005

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Azoospermia
Retinal Degeneration
Pantothenate Kinase-Associated Neurodegeneration
Retina
Electroretinography
Globus Pallidus
Spermatids
Dystonia
Spermatogenesis
Coenzyme A
Deglutition Disorders
Basal Ganglia
Constriction
Knockout Mice
Neurodegenerative Diseases
Spermatozoa
Microscopy
Mitochondria
Central Nervous System
Cell Count

ASJC Scopus subject areas

  • Genetics

Cite this

Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. / Kuo, Ying Ming; Duncan, Jacque L.; Westaway, Shawn; Yang, Haidong; Nune, George; Xu, Eugene Yujun; Hayflick, Susan; Gitschier, Jane.

In: Human Molecular Genetics, Vol. 14, No. 1, 01.01.2005, p. 49-57.

Research output: Contribution to journalArticle

Kuo, Ying Ming ; Duncan, Jacque L. ; Westaway, Shawn ; Yang, Haidong ; Nune, George ; Xu, Eugene Yujun ; Hayflick, Susan ; Gitschier, Jane. / Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 1. pp. 49-57.
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