Phenotypes Associated with This Genotype

Genotype
MGI:3799268

• Allelic Composition: Fas^lpr/Fas^lpr
• Genetic Background: C3.MRL-Fas^lpr

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

immune system

salivary gland inflammation ( J:1028 )

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

abnormal interleukin level ( J:8267 )

• stimulation with concanavalin A does not induce cells to produce Il2

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:1028 )

N • submandibular gland inflammation is observed in most mice at 5 months, but differences compared to wild-type are not significant

N • no parotid gland inflammation is observed and only 1 animal showed sublingual gland inflammation at 5 months

N • in inflamed lacrimal glands, lobular boundaries are preserved with preservation of interlobular septae; lobular atrophy occurs with preservation of ductal epithelium; widely dilated ducts indicate that ductal obstruction is not observed

salivary gland inflammation ( J:1028 )

lacrimal gland atrophy ( J:1028 )

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

hematopoietic system

abnormal T cell morphology ( J:8267 )

• lymph node cells (T cell origin) are abnormal; cells are Ly-2^-/L3T4^-/surface Ig^-

abnormal T cell physiology ( J:8267 )

• cells do not generate CTL in response to stimulation with alloantigens

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

vision/eye

lacrimal gland atrophy ( J:1028 )

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

lacrimal gland inflammation ( J:1028 )

• at 2 months, glandular inflammation is neglible; at 5 months, nearly all mice exhibit lacrimal gland inflammation covering a larger area than in mutants at 2 months or controls at 5 months

• inflammation correlates with age, immune complex level and spleen weight; antinuclear antibody level correlation is greater than probability cutoff; controls do not show correlations with these factors and gland inflammation

• inflammatory infiltrates consist of mononuclear cells and occurs in a periductal or perivascular pattern

• scattered lobular atrophy with loss of secretory elements is seen in glands with multifocal infiltrates

digestive/alimentary system

salivary gland inflammation ( J:1028 )

cellular

decreased apoptosis ( J:114219 )

• unlike wild-type vaginal cells, vaginal cells derived from mutant mice do not undergo apoptosis after treatment with agonistic anti-mouse Fas antibody or mouse recombinant TNF antibody

decreased neuron apoptosis ( J:124252 )

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

abnormal T cell proliferation ( J:8267 )

• cells do not proliferate in response to stimulation with alloantigens

nervous system

decreased neuron apoptosis ( J:124252 )

• neuron viability is comparable to wild-type when grown in absence of Abeta or if treated with KCN which induces necrotic cell death

• very low levels of apoptosis (15%) compared to wild-type (60%) are seen when cortical neurons are treated with Abeta25-35 or Abeta1-40 peptides

reproductive system

abnormal vagina weight ( J:114219 )

♀ • at 2 days after estrogen deprivation induced by gonadectomy, mutant females show no vaginal regression (measured by a decrease in vaginal organ weight), indicating no Fas-mediated vaginal cell death, in contrast to wild-type females that show >50% decrease in vaginal organ weight

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:1028