A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

Abstract

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx−/−), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx−/−mouse exhibit morphology as in the wild type mouse. In addition, the SCN contain vasoactive intestinal peptide-, vasopressin-, and gastrin-releasing peptide-immunoreactive neurons as present in the wild type. Anterograde in vivo tracings from the retina of the Crx−/− and wild type mouse showed that the retinohypothalamic projection to the SCN and the central optic pathways were similar in both animals. Telemetric monitoring of the running activity and temperature revealed that both the Crx−/−and wild type mouse exhibited diurnal rhythms with a 24-h period, which could be phase changed by light. However, power spectral analysis revealed that both rhythms in the Crx−/− mouse were less robust than those in the wild type. The normal development of the SCN and the central visual pathways in the Crx−/− mouse suggests that a modulatory input from the photoreceptors in the peripheral retina to the retinal melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx−/− mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse.

A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse

“…system (Data Sciences International) as previously described (Rovsing et al . ). Mice were kept for 9 days in LD and for 7 days in DD.…”

Crx broadly modulates the pineal transcriptome

“…In contrast to the absence of marked morphological changes in the pineal gland, the retina of Crx −/− mice is grossly affected as evident from the loss of photoreceptor outer segments (Furukawa et al. 1999; Rovsing et al. 2010).…”

“…This may reflect temporal disorganization of the transcription factor system which controls gene expression, including Cry1 and Nr1d1/Rev‐erbα. It is also possible that this is linked to the less robust nature of circadian locomotor activity seen in the Crx −/− mouse (Rovsing et al. 2010), which provides evidence for a role of Crx in circadian rhythms, separate from phenotype determination in the pineal gland and retina.…”

“…1999) but not the non‐image‐forming visual system controlling circadian rhythms (Panda et al. 2003; Rovsing et al. 2010).…”

“…2010). Crx −/− mice exhibit suppressed circadian rhythms in locomotor activity, suggesting that Crx may directly or indirectly alter retinal ganglion cell output, the suprachiasmatic nucleus, other structures controlling locomotor activity, or a combination (Rovsing et al. 2010).…”