Comparative anatomy of mouse and human nail units

Abstract

Recent studies of mice with hair defects have resulted in major contributions to the understanding of hair disorders. To use mouse models as a tool to study nail diseases, a basic understanding of the similarities and differences between the human and mouse nail unit is required. In this study we compare the human and mouse nail unit at the macroscopic and microscopic level and use immunohistochemistry to determine the keratin expression patterns in the mouse nail unit. Both species have a proximal nail fold, cuticle, nail matrix, nail bed, nail plate, and hyponychium. Distinguishing features are the shape of the nail and the presence of an extended hyponychium in the mouse. Expression patterns of most keratins are similar. These findings indicate that the mouse nail unit shares major characteristics with the human nail unit and overall represents a very similar structure, useful for the investigation of nail diseases and nail biology.

Fig. 1. Foot/nail surface orientation

The mouse walks on its feet with the plantar and palmar pads on the surface (a and b). Through extension in the proximal metacarpointerphalangeal joint and flexion in the proximal interphalangeal joint the nail tips are in contact with the surface (b). Lateral view of the nail relative to the distal phalanx postmortem reveals that the nail arcs up, then down, such that the nail does not touch the surface when all the muscles are relaxed (c). MicroCT-Scan of the middle and distal phalanx bones of the third mouse digit (d and e). The 3D reconstruction (d) and sagittal section (e) show that the dorsal angle of the distal interphalangeal joint is almost ninety degrees.

Fig. 2. Differentiating front from rear feet

The front feet (a, b) are smaller than the rear and D I is rudimentary when viewed in either the dorsal (a) or palmar (b) surface. By contrast, the rear feet (c, d) have longer digits and a prominent D I which is shorter than D V and enables orientation. Bar = 1mm.

Fig. 3. Macroanatomy of the human nail and mouse unit

Dorsal view of the human nail unit (a) illustrates the nail plate, proximal nail fold (pnf), lateral nail folds (lnf), lunula (lu), and cuticle (cu). Lateral view (b) illustrates the slightly curved, dorsoventrally flattened plate of the human nail. Dorsal view of the mouse nail unit (c) illustrates the proximal nail fold (pnf), lunula (l), cuticle (cu), but no lateral nail fold. Lateral view (d) illustrates the more prominent curvature of the mouse nail and the complete covering of the lateral side of the distal phalanx by the nail plate. Arrowhead (d) indicates prominent vessel visible through the nail plate. (c) bar = 0.5mm; (d) bar = 1mm.

Fig. 4. Scanning electron microscopy of the mouse nail unit

SEM provides detailed 3 dimensional images of the nail unit. Note that structures beneath the nail plate, namely the lunula and vessels, are not visible by this method. (a) Side view illustrates the long hair covering the proximal nail fold. Note the longitudinal curvature and pointed tips of the nails. (b) Ventral view shows the structured undersurface of the digits with the prominent digit pads and interdigital pads. (c) Dorsal view of the nail shows the surface of the nail plate, which is built of flattened cornified cells. (d) At higher magnification the free edges of the nail plate and the hyponychium are clearly distinguishable at the undersurface of the nail plate. (e) The nail plate surface at high magnification shows flat polygonal cells. (f) At the digit pad surface cell borders are not clearly visible. Note the high density of openings of eccrine gland ducts (arrow). (a,b) bars = 2mm; (c) bar = 500µm; (d) bar=300µm,(e,f) bars = 25µm

Fig. 5. Light microscopy of the nail unit. The human nail unit (a–f)

(a) Sagittal section through the distal part of a human newborn digit. (b–f) Higher magnification of the boxed areas in (a). (a) The nail plate (np) covers the dorsal surface of the distal digit and extends over its free edge. The nail plate invaginates proximally into the proximal nail fold (pnf). The region of nail matrix (nm), nail bed (nb) and hyponychium (hn) are marked by square brackets. The cuticle (cu) (a and b) is a layer of cornified cells that attaches to the dorsal surface of the nail plate and is produced by keratinocytes of the tip of the proximal nail fold and the eponychium (en), the epithelium covering the ventral surface of the proximal nail fold that shows a prominent granular layer but no papillae (b, insert). At the blunt, free end of the nail plate (a,f) cornified layers of the hyponychium are attached to the under surface of the nail plate. The nail matrix (c, d) is represented by a thickened epithelium at the base of the nail plate starting at the point where the eponychium with its granular layer ends (c, arrow) extending distally to the nail bed which is marked by reduction of cell layers (d, arrowhead). The hyponychium starts where the nail detaches from the nailbed, visible by the appearance of a granular layer (e, arrow). It extends to the distal grove (dg) (a). (a) bar = 1mm; (b–f) bars = 100 µm. The mouse nail unit (g–l). (g) Sagittal section through the distal part of an adult mouse nail unit. (h–l) Higher magnification of the boxed areas in (g). The region of nail matrix (nm), nail bed (nb) and hyponychium (hn) are marked by a continuous, dotted, and dashed line, respectively. Arrows in (c,e,i, and k) indicate the onset of the granular layer; (h) shows the eponychium (en) that contributes to the cuticle (cu). Insert in (i) shows a higher magnification of the boxed area with the loss of the granular layer at the transition to the apical matrix (am). Arrow tip in (i) indicates loss of granular layer (onset of onycholemmal keratinization) at the transition from nail matrix to nail bed. Arrow tip in (k) indicates reappearance of granular layer at the transition from nail bed to hyponychium. (g) bar = 500 µm; (h–l) bars = 100µm; (i, inset) bar = 50µm. Cartoons illustrate a median-sagittal section through the human and mouse nail unit, demonstrating comparative structures of both nail units.

Fig. 6. Transverse section through human and mouse nail bed

(a) Transverse section of the human nail bed (nb) illustrates the deep interdigitations between epithelium and the underlying dermis. (Reproduced from Zaias, 1990, with permission) (b) Transverse section through the mouse nail bed shows a flatter, laterally pronounced papillary pattern of the nail bed epithelium. Arrows denote the onset of the granular layer of the hyponychium. np, nail plate. Bar = 40 µm

Fig. 7. Keratin expression in the mouse nail unit

Longitudinal sections through the mouse nail unit were labeled with antibodies against KRT5 (a,g), KRT14 (b,h), KRT17 (c,e,i), KRT6A (d,f,j), KRT1 (k,l), KRT10 (m,n) and acidic hair keratins detected with the monoclonal mouse antibody AE13 (o, o’). (a–e,k,m,o) show the proximal aspect of the nail unit including apical matrix (am), ventral matrix (vm), eponychium (en) and nail plate (np). (g–j,l,n) show the distal aspect of the nail unit consisting of the nail bed (nb) and the hyponychium (hn). KRT5 (a), KRT14 (b) and KRT17 (c) show a very similar pattern in the nail matrix and the eponychium. However, KRT17 is often detectable only in occasional cells in the distal matrix (c, inset) and in limited areas of the hyponychium (i). KRT6A (d) is expressed in the apical matrix but not in the ventral matrix. (e,f) show a higher magnification of the nail bed where suprabasally located KRT17 (e) and KRT6A (f) positive cells (arrow heads) were detectable. (g) shows the basal expression of KRT5 in the hyponychium, whereas K14 (h) shows a panepidermal pattern. Note the patchy pattern of KRT17 (i) in the same region. (j) KRT6A shows panepidermal labeling of the hyponychium. KRT1 labeling in the proximal (k) and distal (l) nail unit shows a strong panepidermal expression of the eponychium and suprabasal expression of the hyponychium but no labeling of nail matrix or nail bed. Note that the apical matrix also shows basal labeling (k, inset) and that in the hyponychium the labeling reaches in some areas the basal layer (l, inset). KRT10 shows a pattern similar to that of KRT1, but less extension to the basal layer (m,n, insets). AE13 labeling illustrates the expression of hard keratins in the suprabasal layers of the nail matrix (o, o’). np, nail plate. Dashed lines, border between dermis and epidermis. Bars = 50 µm

Fig. 8. Comparison of keratin expression in the human and mouse nail unit

Human studies were summarized from: Perrin et al. (Perrin et al., 2004), McGowan et al. (McGowan and Coulombe, 2000) and De Berker et al. (De Berker et al., 2000). b, basal layer; sb, suprabasal layer(s); kgz, keratogenous zone; grey = weak or scattered expression; bold = our study; regular = published studies. *KRT16 has not been studied in the mouse nail unit.¹ (Wojcik et al., 2001), ² (Gu and Coulombe, 2007), ³ (Tong and Coulombe, 2004), ⁴ (Wang et al., 2003), ^#detected with AE13.