| First Author | Bronson RT | Year | 1990 |
| Journal | Mouse Genome | Volume | 87 |
| Pages | 110 | Mgi Jnum | J:79052 |
| Mgi Id | MGI:2387042 | Citation | Bronson RT, et al. (1990) Harlequin (Hq) produces progressive cerebellar cortical atrophy. Mouse Genome 87:110 |
| abstractText | Full text of Mouse Genome contribution: HARLEQUIN (Hq) PRODUCES PROGRESSIVE CEREBELLAR CORTICAL ATROPHY. Roderick T. Bronson, Priscilla W. Lane, Belinda S. Harris and Muriel T. Davisson; The Jackson Laboratory, Bar Harbor, ME 04609 INTRODUCTION Harlequin (Hq) is an X-linked semidominant mutation first described in 1971 (1.2). Until now it has been known only as an abnormality of the hair coat. Hemizygous males (lHq/Y) and homozygous females (Hq/Hq) are nearly bald, and heterozygous females (Hq+) have a patchy irregular loss of hair. In this report we describe progressive ataxia and cerebellar cortical atrophy in this mutant. MATERIALS AND METHODS A total of 34 mice from the B6CBACa-Aw-J/A-Hq stock were classified by their coat and studied at various ages. All mice were anesthesized with tribromoethanol (Avertin) and sacrificed by intra- cardiac perfusion of physiological saline followed by formol-acid-alcohol or Bouin's fixative. They were processed, after fixation, as follows. The hind brains plus cerebellum of 3 Hq/Y mice, 1.5, 9 and 11 months old were dissected out, embedded in paraffin and serial sectioned. Alternate strips of serial sections were stained with hematoxylin and eosin (H&E) or Luxol-fast-blue plus cresylecht- violet (LFB-CV). From other mice only one or two cross sections of cerebellum including the floccular lobes were prepared and stained with H&E. Spines of two 9 month old Hq/Y mice were dissected out, demineralized in Bouin's solution, cut into at least 6 cross sections along the spine, embedded and sectioned. RESULTS Beginning at 5 months of age Hq/Y males and to a much lesser extent Hq/Hq females began to show mild signs of ataxia, characterized by a side to side unsteady gait and a perceptible lateral tremor when at rest. These abnormalites progressed so that by 9 months of age the males had a pronounced truncal ataxia evidenced by marked lateral swaying both during movement and at rest. They gradually lost weight and were sacrificed by 11 months at the oldest. The HqlHq females never developed more than mild ataxia. Heterozygous females and wild type males and females from the Hq stock were always normal. Four Hq/Y mice at 9-11 months of age had extensive loss of Purkinje and granule cells in all parts of the cerebellum. In all cases the Purkinje cell loss tended to be patchy, some folia being devoid of cells, others having about half their normal complement of Purkinje cells. There was no displacement of Purkinje into molecular and/or granule cell layers. Clear spaces denoting where absent Purkinje cells had been previously, so called Òempty basketsÓ, were not seen, nor was there a significant proliferation of Bergman glia, as seen in some other types of cerebellar atrophy. The granule cell layer was generally uniformly thick, but somewhat thinner than normal with less densely packed granule cells. The cerebella from nine Hq/Hq females ranging in age from 5 to 8 months generally had only very mild patchy loss of Purkinje cells in some folia, and no reduction in granule cells. There was extensive loss of both cell types, however, in the floccular lobes. Some pyknotic nuclei were observed in granule cell layers of the aggected lobes. Six Hq/Y males at 1-1.5 months had normal cerebella as did nine Hq/+ females aged 7-12 months, and two wild type males and two wild type females at 12 months. In no mouse in the study were there abnormalities in any other part of the brain or spinal cord. DISCUSSION Nueronal loss in cerebellum is common to many neurological mouse mutants, including Purkinje cell degeneration, lurcher, and weaver. In these it occurs very early in life and is associated with various other abnormalities such as abnormal granule cell migration. Harlequin, like beige, is unusual in the degenerative changes develop only slowly over time (3). Genetically the neurological phenotype is different from the dermatological one. While homozygous females have the same nearly nude phenotype as hemizygous males, they have only a partial cerebellar atrophy, unlike males in which the cerebellar atrophy is severe. Moreover, heterozygous females exhibit a patchy loss of hair but have normal cerebella. REFERENCES 1. Barber. B.R. 1971. Mouse News Lett. 45:34. 2. Falconer, D.S., and J.H. Isaacson. 1972. Mouse News Lett. 47:28. 3. Murphy, E.D., and J.B. Roths. 1978. Jackson Lab. Ann. Rep. 49:108. |
