All Phenotypes Asnsd1<Gt(OST460318)Lex> MGI Mouse

lethality at weaning, incomplete penetrance ( J:320329 )

• mice exhibit moderately reduced viability at weaning; cause is not determined but may be related to seizures

decreased grip strength ( J:320329 )

• grip strength is significantly reduced at 5 and 11 weeks of age

environmentally induced seizures ( J:320329 )

• approximately half of mice exhibit severe handling-associated seizures between 3 and 12 months of age

• however, no histologic lesions are detected in brain

increased percent body fat/body weight ( J:320329 )

• mice exhibit a striking increase in normalized body fat percentage on both a normal chow and a high-fat diet

decreased lean body mass ( J:320329 )

• chow-fed mice show significantly decreased lean body mass relative to diet-matched controls

• however, both male and female mice exhibit normal body weights

abnormal limb muscle morphology ( J:320329 )

• in the 14- week-old hindlimb, marked replacement of myocytes by adipocytes is noted in the vastus lateralis and tensor fascia latae muscles, whereas adipocytes are relatively uncommon in other proximal leg muscles

• adipocytes in the rectus femoris muscle appear in clusters

abnormal skeletal muscle fiber morphology ( J:320329 )

• at 14 weeks of age, less severely affected atrophic fibers exhibit disordered myofibril alignment and disrupted banding patterns; numerous type II myocytes show loss of normal myosin banding pattern

• fast-twitch (type II) fibers are more susceptible to degeneration and transdifferentiation into adipose tissue than slow-twitch (type I) fibers

centrally nucleated skeletal muscle fibers ( J:320329 )

• at 14 weeks of age, the majority of skeletal myocytes have centralized nuclei

skeletal muscle fiber degeneration ( J:320329 )

• at 14 weeks of age, many but not all muscle groups examined exhibit extensive mild degenerative changes: scattered individual and small groups of muscle fibers show features of degeneration, including internalized nuclei, hypereosinophilia (hyaline degeneration), and loss of cross-striations

• at early stages, individual hypereosinophilic degenerating fibers show extensive rearrangement and loss of normal banding patterns of both myosin and desmin

• by 37 weeks of age, severely affected muscles show scattered clusters of rounded atrophic fibers with centralized nuclei while degenerating myocytes are surrounded by abundant mature white adipocytes

skeletal muscle fiber necrosis ( J:320329 )

• at 14 weeks of age, some degenerating skeletal muscle fibers progress to necrosis with disrupted flocculated sarcoplasm and occasional intracellular macrophages; both heavy chain myosin and desmin are typically absent in necrotic myocytes

decreased skeletal muscle mass ( J:320329 )

• mice develop severe sarcopenia

enhanced skeletal muscle regeneration ( J:320329 )

• at 37 weeks of age, morphological signs of skeletal muscle regeneration (small-diameter regenerating fibers with rows of centralized MyoD/Myogenin-positive nuclei), are detected only in the diaphragm

muscle weakness ( J:320329 )

• at 5 and 11 weeks of age, almost all mice fall off the screen immediately in an inverted screen assay, indicating muscle weakness

myopathy ( J:320329 )

• mice develop degenerative myopathy with extensive replacement of skeletal myocytes by adipocytes

• at 14 weeks of age (early stages), the extent of myosteatosis is generally mild but varies among muscles

• by 37 weeks of age, the severity and extent of sarcopenia with intramuscular and interstitial steatosis is markedly increased

• myopathic lesions are restricted to type II (fast twitch) muscle fibers; mixed fiber type muscles (e.g., vastus intermedius and soleus) are largely spared

• however, only minimal inflammation, fibrosis, and muscle regeneration are observed

cardiovascular system phenotype ( J:320329 )

N	• 14- and 37-week-old mice exhibit no histological evidence of steatosis or lipotoxicity in the heart

decreased systemic arterial systolic blood pressure ( J:320329 )

• systolic blood pressure is significantly decreased at 12 weeks of age

• however, no notable lesions are detected in the heart

abnormal cell differentiation ( J:320329 )

• myopathy is associated with extensive transdifferentiation and replacement of muscle by well-differentiated adipose tissue

homeostasis/metabolism phenotype ( J:320329 )

N	• 12-week-old mice show no differences in fed serum chemistry levels (including sodium, calcium, phosphate, glucose, creatinine, and total bilirubin levels) relative to wild-type controls; fasting serum glucose levels are also normal

increased circulating alanine transaminase level ( J:320329 )

• serum ALT level is significantly increased at 12 weeks of age