Analysis Tools
mortality/aging
|
• increased death rate starting at 2 weeks of age, partly due to infections associated with acquired immunodeficiency
• 100% survival rate over 49 days on a supplemented (Ensure Plus shake) diet
|
growth/size/body
|
• some mice develop snout skin erosions, possibly due to impaired healing of abrasions
|
|
• oral lesions similar to those seen in humans with pemphigus vulgaris
• however, no evidence for acantholysis or separation of the suprabasilar epithelium is observed
|
|
• desmoplakin and plakoglobin are reduced within adult tongue tissues
• tongue lesions with loss of suprabasilar epithelium
|
|
• bloated intestines
• however, the colon and the large and small intestines appear normal
|
|
• decreased body size (runting) at P15 to P19, but not prior to P12
|
|
• mice develop a severe wasting syndrome starting at 2 weeks of age that results in runting and reduced body fat deposition
• severe wasting leads to acquired immunodeficiency
• mice become markedly emaciated with age
• both wasting and immunodeficiency are reversed by diet (Ensure Plus shake) supplementation
|
|
• growth rate begins to lag at P12 to P14
|
respiratory system
|
• obstructed upper airways consistent with the observed inspiratory stridor
• obstructions within the pharynx probably limit food intake, leading to malnutrition
|
|
• abnormally increased thickness of epithelial layers in the laryngeal areas, esp. the stratum spinosum, leading to severe airway obstruction
|
|
• laryngeal cartilage deformities
|
|
• epiglottis is significantly hyperplasic, amorphous, and enlarged
|
|
• epiglottis hyperplasia leads to its deformation and thickening, resulting in a narrowed laryngeal opening
• liquid diet supplementation does not reduce hyperplasia of the epiglottis
|
|
• severe hyperplasia of the subglottic epithelium
|
|
• epiglottis hyperplasia leads to its deformation and thickening, resulting in a narrowed laryngeal opening
|
|
• subglottic stenosis due to severe hyperplasia of the subglottic epithelium
|
|
• marked thickening of the pseudostratified ciliated columnar epithelium in trachea cross sections at 6 months of age
|
|
• runted adult mice with hair loss exhibit labored breathing
|
|
• adult mice exhibit characteristic inspiratory stridor (squeaking), due to airway obstructions and thickened epithelial layers
|
immune system
|
• significantly increased frequency of splenic neutrophils with high forward and side light scatter properties in adult mice
|
|
• significantly reduced lymphocyte numbers within the thymus and spleen between 4 and 24 weeks of age
|
|
• dramatic reduction in CD4+CD8+ double-positive thymocytes after 3 weeks of age
|
|
• significantly reduced B cells in spleen between 4 and 24 weeks of age
• liquid diet supplementation reverses pre-B and immature B-cell numbers in both the spleen and bone marrow
|
|
• dramatic reduction in CD93+ immature B cells in the bone marrow
|
|
• reduction of CD93+ immature/transitional B cells in the spleen
|
|
• dramatic reduction in IgM-B220+ pre-B cells in the bone marrow
|
|
• significantly reduced CD4+ and CD8+ single-positive T cells in spleen between 4 and 24 weeks of age
|
integument
|
• the skin subcutaneous fat layer is dramatically reduced in thickness
|
|
• some mice develop snout skin erosions, possibly due to impaired healing of abrasions
|
|
• by P17-P18, mice develop a thinning of the hair coat characterized by a bald spot on the head, which then progresses from head to tail by P25 to P27
• new hair growth is seen on the head area where hair loss was first noted, which then progresses from head to tail in a pattern similar to the hair loss
• mice recover nearly normal hair coats at P32 to P35; a second, less synchronized, hair loss cycle begins at P36 to P38
|
|
• older mice exhibit a patchy appearance with variable sized bald spots at random locations
|
sparse hair
(
J:219200
)
|
• thinning of the hair coat beginning on the head by P17 to P18
|
|
• inflammation and thickening of the epidermis, esp. of the stratum spinosum, in snout tissue cross sections
• hyperplasia of the stratum spinosum in sections of larynx epithelium
|
|
• epidermal thickening of the stratum spinosum in snout tissue cross sections
|
|
• tongue lesions with loss of suprabasilar epithelium
|
|
• in response to mechanical stress (shaking), neonatal skin keratinocytes grown as confluent cell monolayers show an ~80% increase in the number of monolayer fragments, indicating altered mechanical integrity
|
skeleton
|
• laryngeal cartilage deformities
|
|
• epiglottis is significantly hyperplasic, amorphous, and enlarged
|
|
• epiglottis hyperplasia leads to its deformation and thickening, resulting in a narrowed laryngeal opening
• liquid diet supplementation does not reduce hyperplasia of the epiglottis
|
|
• ~2% of mice develop dorsa-ventral rib cage flattening
|
digestive/alimentary system
|
• oral lesions similar to those seen in humans with pemphigus vulgaris
• however, no evidence for acantholysis or separation of the suprabasilar epithelium is observed
|
|
• desmoplakin and plakoglobin are reduced within adult tongue tissues
• tongue lesions with loss of suprabasilar epithelium
|
|
• epiglottis is significantly hyperplasic, amorphous, and enlarged
|
|
• epiglottis hyperplasia leads to its deformation and thickening, resulting in a narrowed laryngeal opening
• liquid diet supplementation does not reduce hyperplasia of the epiglottis
|
|
• bloated intestines
• however, the colon and the large and small intestines appear normal
|
craniofacial
|
• some mice develop snout skin erosions, possibly due to impaired healing of abrasions
|
|
• oral lesions similar to those seen in humans with pemphigus vulgaris
• however, no evidence for acantholysis or separation of the suprabasilar epithelium is observed
|
|
• desmoplakin and plakoglobin are reduced within adult tongue tissues
• tongue lesions with loss of suprabasilar epithelium
|
adipose tissue
|
• the skin subcutaneous fat layer is dramatically reduced in thickness
|
|
• reduced body fat reminiscent of a starvation phenotype
|
hematopoietic system
|
• significantly increased frequency of splenic neutrophils with high forward and side light scatter properties in adult mice
|
|
• significantly reduced lymphocyte numbers within the thymus and spleen between 4 and 24 weeks of age
|
|
• dramatic reduction in CD4+CD8+ double-positive thymocytes after 3 weeks of age
|
|
• significantly reduced B cells in spleen between 4 and 24 weeks of age
• liquid diet supplementation reverses pre-B and immature B-cell numbers in both the spleen and bone marrow
|
|
• dramatic reduction in CD93+ immature B cells in the bone marrow
|
|
• reduction of CD93+ immature/transitional B cells in the spleen
|
|
• dramatic reduction in IgM-B220+ pre-B cells in the bone marrow
|
|
• significantly reduced CD4+ and CD8+ single-positive T cells in spleen between 4 and 24 weeks of age
|
reproductive system
|
• female homozygotes are unable to maintain viable litters
|
homeostasis/metabolism
|
• serum leptin levels are significantly reduced
|
vision/eye
